NM_000321.3(RB1):c.1695+5G>A AND Retinoblastoma

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 25, 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:: RCV003516354.1

Allele description

NM_000321.3(RB1):c.1695+5G>A

Gene:

RB1:RB transcriptional corepressor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.2

Genomic location:

Preferred name:

NM_000321.3(RB1):c.1695+5G>A

HGVS:

NC_000013.11:g.48381448G>A
NG_009009.1:g.82702G>A
NM_000321.3:c.1695+5G>AMANE SELECT
NM_001407165.1:c.1695+5G>A
NM_001407166.1:c.1700G>A
NP_001394095.1:p.Ser567Asn
LRG_517:g.82702G>A
NC_000013.10:g.48955584G>A

Protein change:

S567N

Molecular consequence:

NM_000321.3:c.1695+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407165.1:c.1695+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407166.1:c.1700G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Retinoblastoma (RB1)
Synonyms:: Eye cancer, retinoblastoma; RETINOBLASTOMA, SOMATIC
Identifiers:: MONDO: MONDO:0008380; MeSH: D012175; MedGen: C0035335; Orphanet: 790; OMIM: 180200; Human Phenotype Ontology: HP:0009919

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Homo sapiens clone 25100 mRNA sequence, complete cds
Homo sapiens clone 25100 mRNA sequence, complete cds
gi|4406606|gb|AF131780.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004297225	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 25, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17576681, 9536098, 14722923, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297225

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 25, 2023)

germline

clinical testing

PubMed (4)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004297225.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is also known as g.78284G>A. This variant has been observed in individual(s) with retinoblastoma (PMID: 14722923; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 17 of the RB1 gene. It does not directly change the encoded amino acid sequence of the RB1 protein. It affects a nucleotide within the consensus splice site.

#	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: Feb 20, 2024

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