rs1340503453

Variant names:

• chr13-48348947-G-A
• NM_000321.3:c.540-9G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-48348947-G-A
• chr13-48348947-G-C
• chr13-48348947-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_000321.3(RB1):​c.540-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RB1 NM_000321.3 intron
• Scores: Splicing: ADA: 0.003389
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.667

Genes affected

RB1 (HGNC:9884): (RB transcriptional corepressor 1) The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 13-48348947-G-A is Benign according to our data. Variant chr13-48348947-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1940356.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RB1	NM_000321.3	c.540-9G>A		intron_variant	Intron 5 of 26	ENST00000267163.6	NP_000312.2
RB1	NM_001407165.1	c.540-9G>A		intron_variant	Intron 5 of 26		NP_001394094.1
RB1	NM_001407166.1	c.540-9G>A		intron_variant	Intron 5 of 16		NP_001394095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.540-9G>A		intron_variant	Intron 5 of 26	1	NM_000321.3	ENSP00000267163.4
RB1	ENST00000467505.5	n.138-11070G>A		intron_variant	Intron 1 of 2	1		ENSP00000434702.1
RB1	ENST00000650461.1	c.540-9G>A		intron_variant	Intron 5 of 26			ENSP00000497193.1
RB1	ENST00000525036.1	n.702-9G>A		intron_variant	Intron 5 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinoblastoma Benign:1

Feb 16, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0034
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-48923083;