chr13-48461331-T-C

Position:

• chr13-48461331-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.2106+1498T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,176 control chromosomes in the GnomAD database, including 5,282 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 0.26 (5282 hom., cov: 32)
• Consequence: RB1 NM_000321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RB1	NM_000321.3	c.2106+1498T>C		intron_variant		ENST00000267163.6
RB1	NM_001407165.1	c.2106+1498T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RB1	ENST00000267163.6	c.2106+1498T>C		intron_variant		1	NM_000321.3	P1
RB1	ENST00000643064.1	c.194+79888T>C		intron_variant
RB1	ENST00000650461.1	c.2106+1498T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39760 AN: 152058 Hom.: 5283 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.261 AC: 39771 AN: 152176 Hom.: 5282 Cov.: 32 AF XY: 0.262 AC XY: 19490 AN XY: 74408

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.247

Alfa AF: 0.265 Hom.: 715

Bravo AF: 0.261

Asia WGS AF: 0.247 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.0
DANN	Benign	0.88

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: rs198584; hg19: chr13-49035467;