Variant 13-48476876-C-T 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 ENST00000267163.6(RB1):c.2663+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,609,814 control chromosomes in the GnomAD database, including 759,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.91 ( 63708 hom., cov: 32)

Exomes 𝑓: 0.98 ( 696186 hom. )

Consequence

RB1
ENST00000267163.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.309

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 13-48476876-C-T is Benign according to our data. Variant chr13-48476876-C-T is described in ClinVar as [Benign]. Clinvar id is 255823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RB1	NM_000321.3 linkuse as main transcript	c.2663+33C>T	intron_variant	ENST00000267163.6	NP_000312.2
RB1	NM_001407165.1 linkuse as main transcript	c.2663+33C>T	intron_variant		NP_001394094.1
RB1	NM_001407168.1 linkuse as main transcript	c.113+33C>T	intron_variant		NP_001394097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6 linkuse as main transcript	c.2663+33C>T		intron_variant		1	NM_000321.3	ENSP00000267163	P1

Frequencies

GnomAD3 genomes

AF:

0.908

AC:

138080

AN:

152124

Hom.:

63670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.998

Gnomad AMR

AF:

0.932

Gnomad ASJ

AF:

0.938

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.956

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.985

Gnomad OTH

AF:

0.926

GnomAD3 exomes

AF:

0.958

AC:

240487

AN:

250916

Hom.:

115844

AF XY:

0.963

AC XY:

130625

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.717

Gnomad AMR exome

AF:

0.950

Gnomad ASJ exome

AF:

0.932

Gnomad EAS exome

AF:

0.997

Gnomad SAS exome

AF:

0.956

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.985

Gnomad OTH exome

AF:

0.963

GnomAD4 exome

AF:

0.976

AC:

1423086

AN:

1457572

Hom.:

696186

Cov.:

AF XY:

0.976

AC XY:

708124

AN XY:

725364

show subpopulations

Gnomad4 AFR exome

AF:

0.715

Gnomad4 AMR exome

AF:

0.949

Gnomad4 ASJ exome

AF:

0.934

Gnomad4 EAS exome

AF:

0.998

Gnomad4 SAS exome

AF:

0.957

Gnomad4 FIN exome

AF:

0.998

Gnomad4 NFE exome

AF:

0.987

Gnomad4 OTH exome

AF:

0.960

GnomAD4 genome

AF:

0.908

AC:

138177

AN:

152242

Hom.:

63708

Cov.:

AF XY:

0.911

AC XY:

67836

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.726

Gnomad4 AMR

AF:

0.932

Gnomad4 ASJ

AF:

0.938

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.956

Gnomad4 FIN

AF:

0.999

Gnomad4 NFE

AF:

0.985

Gnomad4 OTH

AF:

0.926

Alfa

AF:

0.972

Hom.:

122501

Bravo

AF:

0.896

Asia WGS

AF:

0.957

AC:

3330

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

Retinoblastoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.2

DANN

Benign

0.46

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