Variant 13-48345222-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000321.3(RB1):c.500+23T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 1,606,016 control chromosomes in the GnomAD database, including 762,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66838 hom., cov: 31)

Exomes 𝑓: 0.98 ( 695635 hom. )

Consequence

RB1
NM_000321.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.319

Variant links:

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]

RB1 links:

RB1 (HGNC:):

RB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 13-48345222-T-G is Benign according to our data. Variant chr13-48345222-T-G is described in ClinVar as [Benign]. Clinvar id is 255825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RB1	NM_000321.3 linkuse as main transcript	c.500+23T>G	intron_variant	ENST00000267163.6	NP_000312.2	P06400A0A024RDV3
RB1	NM_001407165.1 linkuse as main transcript	c.500+23T>G	intron_variant		NP_001394094.1
RB1	NM_001407166.1 linkuse as main transcript	c.500+23T>G	intron_variant		NP_001394095.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RB1	ENST00000267163.6 linkuse as main transcript	c.500+23T>G	intron_variant	1	NM_000321.3	ENSP00000267163.4	P06400
RB1	ENST00000467505.5 linkuse as main transcript	n.138-14795T>G	intron_variant	1		ENSP00000434702.1	Q92728
RB1	ENST00000650461.1 linkuse as main transcript	c.500+23T>G	intron_variant			ENSP00000497193.1	A0A3B3IS71
RB1	ENST00000525036.1 linkuse as main transcript	n.662+23T>G	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.934

AC:

142083

AN:

152050

Hom.:

66798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.821

Gnomad AMI

AF:

0.998

Gnomad AMR

AF:

0.944

Gnomad ASJ

AF:

0.938

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.933

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.985

Gnomad OTH

AF:

0.945

GnomAD3 exomes

AF:

0.963

AC:

239336

AN:

248654

Hom.:

115463

AF XY:

0.964

AC XY:

129787

AN XY:

134614

show subpopulations

Gnomad AFR exome

AF:

0.818

Gnomad AMR exome

AF:

0.955

Gnomad ASJ exome

AF:

0.932

Gnomad EAS exome

AF:

0.997

Gnomad SAS exome

AF:

0.932

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.985

Gnomad OTH exome

AF:

0.963

GnomAD4 exome

AF:

0.978

AC:

1421424

AN:

1453848

Hom.:

695635

Cov.:

AF XY:

0.977

AC XY:

706735

AN XY:

723694

show subpopulations

Gnomad4 AFR exome

AF:

0.814

Gnomad4 AMR exome

AF:

0.955

Gnomad4 ASJ exome

AF:

0.934

Gnomad4 EAS exome

AF:

0.998

Gnomad4 SAS exome

AF:

0.934

Gnomad4 FIN exome

AF:

0.998

Gnomad4 NFE exome

AF:

0.987

Gnomad4 OTH exome

AF:

0.965

GnomAD4 genome

AF:

0.934

AC:

142184

AN:

152168

Hom.:

66838

Cov.:

AF XY:

0.936

AC XY:

69631

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.822

Gnomad4 AMR

AF:

0.943

Gnomad4 ASJ

AF:

0.938

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.933

Gnomad4 FIN

AF:

0.999

Gnomad4 NFE

AF:

0.985

Gnomad4 OTH

AF:

0.945

Alfa

AF:

0.953

Hom.:

14212

Bravo

AF:

0.927

Asia WGS

AF:

0.954

AC:

3304

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinoblastoma

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.81

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over