NM_201253.3(CRB1):c.4006-10A>G AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 27, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001056224.6

Allele description [Variation Report for NM_201253.3(CRB1):c.4006-10A>G]

NM_201253.3(CRB1):c.4006-10A>G

Gene:

CRB1:crumbs cell polarity complex component 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_201253.3(CRB1):c.4006-10A>G

HGVS:

NC_000001.11:g.197477654A>G
NG_008483.2:g.281193A>G
NM_001193640.2:c.3670-10A>G
NM_001257965.2:c.3934-10A>G
NM_001257966.2:c.2398-10A>G
NM_201253.3:c.4006-10A>GMANE SELECT
NC_000001.10:g.197446784A>G
NM_201253.2:c.4006-10A>G

Links:

dbSNP: rs766850702

NCBI 1000 Genomes Browser:

rs766850702

Molecular consequence:

NM_001193640.2:c.3670-10A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001257965.2:c.3934-10A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001257966.2:c.2398-10A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_201253.3:c.4006-10A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Retinitis pigmentosa 12 (RP12)
Synonyms:: RP 12; RP WITH OR WITHOUT PPRPE; RP WITH OR WITHOUT PRESERVED PARAARTERIOLE RETINAL PIGMENT EPITHELIUM; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010818; MedGen: C1838647; Orphanet: 791; OMIM: 600105

Name:: Leber congenital amaurosis 8 (LCA8)
Identifiers:: MONDO: MONDO:0013453; MedGen: C3151202; Orphanet: 65; OMIM: 613835

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001220656	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24512366, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001220656

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Retinal Dystrophy with Intraretinal Cystoid Spaces Associated with Mutations in the Crumbs Homologue (CRB1) Gene.

Cordovez JA, Traboulsi EI, Capasso JE, Sadagopan KA, Ganesh A, Rychwalski PJ, Neely KA, Brodie SE, Levin AV.

Ophthalmic Genet. 2015;36(3):257-64. doi: 10.3109/13816810.2014.881505.

PubMed [citation]

PMID:: 24512366

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001220656.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change falls in intron 11 of the CRB1 gene. It does not directly change the encoded amino acid sequence of the CRB1 protein. This variant is present in population databases (rs766850702, gnomAD 0.002%). This variant has been observed in individual(s) with clinical features of CRB1-related conditions (PMID: 24512366; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS11-10A>G. ClinVar contains an entry for this variant (Variation ID: 851764). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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