rs399413

Positions:

• chr13-48374433-A-G
• chr13-48374433-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000267163.6(RB1):​c.1215+941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,022 control chromosomes in the GnomAD database, including 29,087 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (29087 hom., cov: 32)
• Consequence: RB1 ENST00000267163.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623

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]

LOC112268118 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RB1	NM_000321.3	c.1215+941A>G		intron_variant		ENST00000267163.6	NP_000312.2
LOC112268118	XR_002957522.2	n.41-193T>C		intron_variant, non_coding_transcript_variant
RB1	NM_001407165.1	c.1215+941A>G		intron_variant			NP_001394094.1
RB1	NM_001407166.1	c.1215+941A>G		intron_variant			NP_001394095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.1215+941A>G		intron_variant		1	NM_000321.3	ENSP00000267163	P1
RB1	ENST00000650461.1	c.1215+941A>G		intron_variant				ENSP00000497193

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87070 AN: 151902 Hom.: 29091 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.612

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.573 AC: 87074 AN: 152022 Hom.: 29087 Cov.: 32 AF XY: 0.575 AC XY: 42764 AN XY: 74308

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.609

Alfa AF: 0.681 Hom.: 16674

Bravo AF: 0.554

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.1
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs399413; hg19: chr13-48948569;