rs4151467

Positions:

• chr13-48345787-T-C

Variant summary

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

The NM_000321.3(RB1):​c.500+588T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 152,254 control chromosomes in the GnomAD database, including 122 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 0.035 (122 hom., cov: 32)
• Consequence: RB1 NM_000321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RB1	NM_000321.3	c.500+588T>C		intron_variant		ENST00000267163.6	NP_000312.2
RB1	NM_001407165.1	c.500+588T>C		intron_variant			NP_001394094.1
RB1	NM_001407166.1	c.500+588T>C		intron_variant			NP_001394095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.500+588T>C		intron_variant		1	NM_000321.3	ENSP00000267163	P1
RB1	ENST00000467505.5	c.138-14230T>C		intron_variant, NMD_transcript_variant		1		ENSP00000434702
RB1	ENST00000650461.1	c.500+588T>C		intron_variant				ENSP00000497193
RB1	ENST00000525036.1	n.662+588T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5316 AN: 152136 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0349 AC: 5318 AN: 152254 Hom.: 122 Cov.: 32 AF XY: 0.0328 AC XY: 2443 AN XY: 74462

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.0399

Gnomad4 ASJ AF: 0.0596

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0527

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0505 Hom.: 265

Bravo AF: 0.0351

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.8
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

Other links and lift over

dbSNP: rs4151467; hg19: chr13-48919923;