VCV000383768.26 - ClinVar

NM_001378454.1(ALMS1):c.2190C>T (p.Phe730=)

Germline

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.

(13)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001378454.1(ALMS1):c.2190C>T (p.Phe730=)

Variation ID: 383768 Accession: VCV000383768.26

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2p13.1 2: 73448717 (GRCh38) [ NCBI UCSC ] 2: 73675844 (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	Jan 28, 2018	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001378454.1:c.2190C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001365383.1:p.Phe730=	synonymous
NM_015120.4:c.2193C>T	NP_055935.4:p.Phe731=	synonymous
NC_000002.12:g.73448717C>T
NC_000002.11:g.73675844C>T
NG_011690.1:g.67965C>T
LRG_741:g.67965C>T
LRG_741t1:c.2193C>T	LRG_741p1:p.Phe731=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000002.12:73448716:C:T

Functional
consequence

The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele
frequency (GMAF)

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.

0.47364 (C)

Allele frequency

The frequency of the allele represented by this VCV record.

Exome Aggregation Consortium (ExAC) 0.59909

The Genome Aggregation Database (gnomAD), exomes 0.60291

Trans-Omics for Precision Medicine (TOPMed) 0.48833

The Genome Aggregation Database (gnomAD) 0.49457

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.49481

1000 Genomes Project 0.52636

Links

ClinGen: CA1713301

dbSNP: rs7598901

VarSome

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.
ALMS1		-	-	GRCh38 GRCh38 GRCh37	6054	6365

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.
not specified	Benign (6)	criteria provided, multiple submitters, no conflicts	Sep 9, 2016	RCV000419167.11
Alstrom syndrome	Benign (4)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000578055.12
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Dec 21, 2018	RCV002429397.2
ALMS1-related disorder	Likely benign (1)	criteria provided, single submitter	Feb 10, 2020	RCV003959913.1
not provided	Benign (1)	criteria provided, single submitter	-	RCV004708867.1

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.	More information 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.
Benign (Aug 01, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Alstrom syndrome Affected status: unknown Allele origin: germline	Phosphorus, Inc. Accession: SCV000679925.1 First in ClinVar: Jan 28, 2018 Last updated: Jan 28, 2018	Number of individuals with the variant: 21
Benign (Sep 09, 2016)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000524286.4 First in ClinVar: Mar 08, 2017 Last updated: Apr 09, 2018	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Mar 21, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000711903.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: p.Phe729Phe in exon 8 of ALMS1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, … (more) p.Phe729Phe in exon 8 of ALMS1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 77.44% (6674/8618) o f East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs7598901). (less) Number of individuals with the variant: 217
Benign (Jul 14, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Alstrom syndrome Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001769053.1 First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021	Sex: mixed
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Alstrom syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000999963.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Likely benign (Feb 10, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	ALMS1-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004773406.1 First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Benign (Dec 21, 2018)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002729445.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005242444.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Alstrom syndrome Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001458911.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001741567.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001921401.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001929520.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001952250.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

p.Phe729Phe in exon 8 of ALMS1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 77.44% (6674/8618) o f East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs7598901).

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs7598901 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001378454.1(ALMS1):c.2190C>T (p.Phe730=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs7598901 ...