Variant 13-48342759-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 NM_000321.3(RB1):c.380+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,330,802 control chromosomes in the GnomAD database, including 39,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3605 hom., cov: 32)

Exomes 𝑓: 0.24 ( 35859 hom. )

Consequence

RB1
NM_000321.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.96

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 13-48342759-C-T is Benign according to our data. Variant chr13-48342759-C-T is described in ClinVar as [Benign]. Clinvar id is 255824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RB1	NM_000321.3 linkuse as main transcript	c.380+45C>T	intron_variant	ENST00000267163.6	NP_000312.2
RB1	NM_001407165.1 linkuse as main transcript	c.380+45C>T	intron_variant		NP_001394094.1
RB1	NM_001407166.1 linkuse as main transcript	c.380+45C>T	intron_variant		NP_001394095.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
RB1	ENST00000267163.6 linkuse as main transcript	c.380+45C>T	intron_variant	1	NM_000321.3	ENSP00000267163	P1
RB1	ENST00000467505.5 linkuse as main transcript	c.138-17258C>T	intron_variant, NMD_transcript_variant	1		ENSP00000434702
RB1	ENST00000650461.1 linkuse as main transcript	c.380+45C>T	intron_variant			ENSP00000497193
RB1	ENST00000525036.1 linkuse as main transcript	n.542+45C>T	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32434

AN:

151694

Hom.:

3610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.342

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.236

AC:

56447

AN:

238912

Hom.:

6860

AF XY:

0.237

AC XY:

30825

AN XY:

129830

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.244

AC:

287744

AN:

1178990

Hom.:

35859

Cov.:

AF XY:

0.243

AC XY:

145832

AN XY:

599146

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.251

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.214

AC:

32432

AN:

151812

Hom.:

3605

Cov.:

AF XY:

0.216

AC XY:

16013

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.187

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.183

Hom.:

662

Bravo

AF:

0.207

Asia WGS

AF:

0.229

AC:

794

AN:

3474

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -

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

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.070

DANN

Benign

0.33

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