VCV000017576.4 - ClinVar

NM_001904.4(CTNNB1):c.133_135del (p.Ser45del)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic; other
Pathogenic (1)

2 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

Clinical impact

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Tier I (Strong) for 2 tumor types

2 out of 2 submissions contributed to this classification

The aggregate somatic clinical impact for this variant for one or more tumor types, using the AMP/ASCO/CAP terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

Oncogenicity

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Oncogenic

This classification is based on the single submission received

The aggregate oncogenicity classification for this variant for one or more tumor types, using the ClinGen/CGC/VICC terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Variant Details

Identifiers

NM_001904.4(CTNNB1):c.133_135del (p.Ser45del)

Variation ID: 17576 Accession: VCV000017576.4

Type and length

Deletion, 3 bp

Location

Cytogenetic: 3p22.1 3: 41224643-41224645 (GRCh38) [ NCBI UCSC ] 3: 41266136-41266138 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Sep 10, 2016	Sep 26, 2017	May 1, 2016
Somatic - Clinical impact	Nov 22, 2025	Nov 22, 2025	Jul 16, 2025
Somatic - Oncogenicity	Aug 11, 2024	Mar 11, 2025	Mar 4, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001904.4:c.133_135del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001895.1:p.Ser45del	inframe deletion
NM_001904.4:c.133_135delTCT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001098209.2:c.133_135del	NP_001091679.1:p.Ser45del	inframe deletion
NM_001098210.2:c.133_135del	NP_001091680.1:p.Ser45del	inframe deletion
NM_001330729.2:c.112_114del	NP_001317658.1:p.Ser38del	inframe deletion
NC_000003.12:g.41224645_41224647del
NC_000003.11:g.41266136_41266138del
NG_013302.2:g.30195_30197del
LRG_1108:g.30195_30197del
LRG_1108t1:c.133_135del	LRG_1108p1:p.Ser45del

... more HGVS ... less HGVS

Protein change

S45del, S38del

Other names

CTNNB1, 3-BP DEL, SER45DEL

Canonical SPDI

NC_000003.12:41224642:CTTCT:CT

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA250690 OMIM: 116806.0001 dbSNP: rs587776850 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 9065402 Fig. 3B to determine the location of this allele on the current reference sequence.

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CTNNB1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	505	992
LOC126806658	-	-	-	GRCh38	-	288

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Carcinoma of colon	Pathogenic (1)	no assertion criteria provided	Mar 21, 1997	RCV000019137.5
Nephroblastoma	other (1)	no assertion criteria provided	May 1, 2016	RCV000505566.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 21, 1997) C Contributing to aggregate classification	no assertion criteria provided	COLORECTAL CANCER, SOMATIC	OMIM Accession: SCV000039425.2 First in ClinVar: Apr 04, 2013 Last updated: Sep 10, 2016	Publications: PubMed (1) PubMed: 9065402 Observation: 1 Collection method: literature only Allele origin: somatic Affected status: not provided more Observation 1 Collection method: literature only Allele origin: somatic Affected status: not provided Comment on evidence: In 2 colorectal cancer (see 114500) cell lines that expressed full-length APC, yet had escaped inhibition of transcriptional activation mediated by beta-catenin and TCF7L2, Morin … (more) In 2 colorectal cancer (see 114500) cell lines that expressed full-length APC, yet had escaped inhibition of transcriptional activation mediated by beta-catenin and TCF7L2, Morin et al. (1997) found a mutation in a downstream component of the APC tumor suppressor pathway, namely in the CTNNB1 gene. Each tumor line had a different mutation: a 3-bp deletion that removed an amino acid (ser45) in one and a C-to-A missense mutation that changed ser33 to tyr (116806.0002) in the other. Analysis of paraffin-embedded archival tissue from the first patient confirmed the somatic nature of this mutation and its presence in the primary tumor before culture. Both mutations affected serines that have been implicated in the downregulation of beta-catenin through phosphorylation. (less)

other 2: Mutations in members of targetable cancer pathways, gene families, or functional groups, regardless of tumor type; (May 01, 2016) C Contributing to aggregate classification	no assertion criteria provided	WILMS TUMOR SOMATIC:c3267_wilms tumor (Somatic mutation)	Donald Williams Parsons Laboratory, Baylor College of Medicine Additional submitter: Donald Williams Parsons Laboratory, Baylor College of Medicine Study: CSER-BASIC3 Accession: SCV000599912.1 First in ClinVar: Sep 26, 2017 Last updated: Sep 26, 2017	Publications: PubMed (1) PubMed: 26822237 Observation: 1 Collection method: clinical testing Allele origin: somatic Affected status: yes Observation 1 Collection method: clinical testing Allele origin: somatic Affected status: yes

Comment:

Variant has Tier I (strong) clinical significance as a diagnostic inclusion criterion in embryonal rhabdomyosarcoma, based on the following evidence: 1) Documented in one or more cancer databases (e.g., St. Jude Pecan, COSMIC, CIViC, OncoKB). 2) Appears in one or more well-established professional guidelines (e.g., World Health Organization [WHO]; National Comprehensive Cancer Network [NCCN]) as providing diagnostic, prognostic, or therapeutic information. 3) Information in the literature supports potential biologic effect of variant (PMID: 9065402). 4) Diagnostic for a specific tumor type/classification based on well-powered studies with expert-level consensus (Evidence Level B; PMIDs: 24436047, 24332040, 22142829).

Comment:

Variant has Tier I (strong) clinical significance as a diagnostic inclusion criterion in adrenal cortex carcinoma, based on the following evidence: 1) Documented in one or more cancer databases (e.g., St. Jude Pecan, COSMIC, CIViC, OncoKB). 2) Appears in one or more well-established professional guidelines (e.g., World Health Organization [WHO]; National Comprehensive Cancer Network [NCCN]) as providing diagnostic, prognostic, or therapeutic information. 3) Information in the literature supports potential biologic effect of variant (PMIDs: 29435196, 30699286). 4) Diagnostic for a specific tumor type/classification based on well-powered studies with expert-level consensus (Evidence Level B; PMIDs: 16140927, 25743702, 27165744, 25490274, 24747642, 38917236, 34410225).

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.	Morin PJ	Science (New York, N.Y.)	1997	PMID: 9065402

Conditions - Somatic

Tumor type Help The tumor type for this variant-condition (RCV) record in ClinVar.	Clinical impact (# of submissions) Help The aggregate somatic clinical impact for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate somatic clinical impact is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Oncogenicity Help The aggregate oncogenicity classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate oncogenicity classification is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the tumor type.	Variation/condition record Help The most recent date that a submitter evaluated this variant for the tumor type.
Neoplasm		Oncogenic criteria provided, single submitter	Mar 4, 2025	RCV004668736.2
Adrenal cortex carcinoma	Tier I (Strong) - diagnostic - supports diagnosis (1)		Jul 16, 2025	RCV006253627.1
Embryonal rhabdomyosarcoma	Tier I (Strong) - diagnostic - supports diagnosis (1)		Jul 27, 2023	RCV006253628.1

Submissions - Somatic

Clinical impact Help The submitted somatic clinical impact for each SCV record. (Last evaluated)	Review Status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Tumor type Help The tumor type for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Help This column includes more information supporting the somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.

Tier I (Strong) - Diagnostic - supports diagnosis (Jul 27, 2023) C Contributing to aggregate classification	criteria provided, single submitter (AMP/ASCO/CAP Guidelines, 2017)	Embryonal rhabdomyosarcoma	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital Accession: SCV007105016.1 First In ClinVar: Nov 22, 2025 Last updated: Nov 22, 2025	Publications: PubMed (4) PubMed: 22142829‚ 24332040‚ 24436047‚ 9065402 Comment: show Variant has Tier I (strong) clinical significance as a diagnostic inclusion criterion in embryonal rhabdomyosarcoma, based on the following evidence: 1) Documented in one or more cancer databases (e.g., St. Jude Pecan, COSMIC, CIViC, OncoKB). 2) Appears in one or more well-established professional guidelines (e.g., World Health Organization [WHO]; National Comprehensive Cancer Network [NCCN]) as providing diagnostic, prognostic, or therapeutic information. 3) Information in the literature supports potential biologic effect of variant (PMID: 9065402). 4) Diagnostic for a specific tumor type/classification based on well-powered studies with expert-level consensus (Evidence Level B; PMIDs: 24436047, 24332040, 22142829). (less) Observation: 1 Collection method: clinical testing Allele origin: somatic Affected status: yes Observation 1 Collection method: clinical testing Allele origin: somatic Affected status: yes

Tier I (Strong) - Diagnostic - supports diagnosis (Jul 16, 2025) C Contributing to aggregate classification	criteria provided, single submitter (AMP/ASCO/CAP Guidelines, 2017)	Adrenal cortex carcinoma	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital Accession: SCV007105539.1 First In ClinVar: Nov 22, 2025 Last updated: Nov 22, 2025	Publications: PubMed (9) PubMed: 16140927‚ 24747642‚ 25490274‚ 25743702‚ 27165744‚ 29435196‚ 30699286‚ 34410225‚ 38917236 Comment: show Variant has Tier I (strong) clinical significance as a diagnostic inclusion criterion in adrenal cortex carcinoma, based on the following evidence: 1) Documented in one or more cancer databases (e.g., St. Jude Pecan, COSMIC, CIViC, OncoKB). 2) Appears in one or more well-established professional guidelines (e.g., World Health Organization [WHO]; National Comprehensive Cancer Network [NCCN]) as providing diagnostic, prognostic, or therapeutic information. 3) Information in the literature supports potential biologic effect of variant (PMIDs: 29435196, 30699286). 4) Diagnostic for a specific tumor type/classification based on well-powered studies with expert-level consensus (Evidence Level B; PMIDs: 16140927, 25743702, 27165744, 25490274, 24747642, 38917236, 34410225). (less) Observation: 1 Collection method: clinical testing Allele origin: somatic Affected status: yes Observation 1 Collection method: clinical testing Allele origin: somatic Affected status: yes

Oncogenicity Help The submitted oncogenicity classification for each SCV record. (Last evaluated)	Review Status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Tumor type Help The tumor type for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Help This column includes more information supporting the somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.

Oncogenic (Mar 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ClinGen/CGC/VICC Guidelines for Oncogenicity, 2022)	Neoplasm	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV005094501.2 First In ClinVar: Aug 11, 2024 Last updated: Mar 11, 2025	Publications: PubMed (2) PubMed: 21084400‚ 9065402 Observation: 1 Collection method: clinical testing Allele origin: somatic Affected status: yes Observation 1 Collection method: clinical testing Allele origin: somatic Affected status: yes

Comment:

Citations for somatic classification of this variant

Title	Author	Journal	Year	Link
Targeted Next Generation Sequencing molecular profiling and its clinical application in adrenocortical cancer.	Cioppi F	European journal of endocrinology	2024	PMID: 38917236
Targeted genomic analysis of 364 adrenocortical carcinomas.	Pozdeyev N	Endocrine-related cancer	2021	PMID: 34410225
Mutation Hotspots in the β-Catenin Gene: Lessons from the Human Cancer Genome Databases.	Kim S	Molecules and cells	2019	PMID: 30699286
Exon 3 mutations of CTNNB1 drive tumorigenesis: a review.	Gao C	Oncotarget	2017	PMID: 29435196
Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma.	Zheng S	Cancer cell	2016	PMID: 27165744
Genomic landscape of paediatric adrenocortical tumours.	Pinto EM	Nature communications	2015	PMID: 25743702
Whole-exome sequencing characterizes the landscape of somatic mutations and copy number alterations in adrenocortical carcinoma.	Juhlin CC	The Journal of clinical endocrinology and metabolism	2015	PMID: 25490274
Integrated genomic characterization of adrenocortical carcinoma.	Assié G	Nature genetics	2014	PMID: 24747642
Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusion-negative tumors.	Shern JF	Cancer discovery	2014	PMID: 24436047
Targeting oxidative stress in embryonal rhabdomyosarcoma.	Chen X	Cancer cell	2013	PMID: 24332040
Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways.	Shukla N	Clinical cancer research : an official journal of the American Association for Cancer Research	2012	PMID: 22142829
Wnt/β-catenin pathway activation in adrenocortical adenomas is frequently due to somatic CTNNB1-activating mutations, which are associated with larger and nonsecreting tumors: a study in cortisol-secreting and -nonsecreting tumors.	Bonnet S	The Journal of clinical endocrinology and metabolism	2011	PMID: 21084400
Mutations of beta-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors.	Tissier F	Cancer research	2005	PMID: 16140927
Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.	Morin PJ	Science (New York, N.Y.)	1997	PMID: 9065402
Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.	Morin PJ	Science (New York, N.Y.)	1997	PMID: 9065402
click to load more citations click to collapse

Text-mined citations for rs587776850 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 30, 2026