rs4151448

Positions:

• chr13-48343537-A-G

Variant summary

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

The NM_000321.3(RB1):​c.380+823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,190 control chromosomes in the GnomAD database, including 2,444 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 0.11 (2444 hom., cov: 32)
• Consequence: RB1 NM_000321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RB1	NM_000321.3	c.380+823A>G		intron_variant		ENST00000267163.6	NP_000312.2
RB1	NM_001407165.1	c.380+823A>G		intron_variant			NP_001394094.1
RB1	NM_001407166.1	c.380+823A>G		intron_variant			NP_001394095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.380+823A>G		intron_variant		1	NM_000321.3	ENSP00000267163	P1
RB1	ENST00000467505.5	c.138-16480A>G		intron_variant, NMD_transcript_variant		1		ENSP00000434702
RB1	ENST00000650461.1	c.380+823A>G		intron_variant				ENSP00000497193
RB1	ENST00000525036.1	n.542+823A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16068 AN: 152072 Hom.: 2417 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0490

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00543

Gnomad OTH AF: 0.0957

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

GnomAD4 genome AF: 0.106 AC: 16152 AN: 152190 Hom.: 2444 Cov.: 32 AF XY: 0.105 AC XY: 7784 AN XY: 74428

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.0453

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0490

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.00541

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0242 Hom.: 508

Bravo AF: 0.119

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.82

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: rs4151448; hg19: chr13-48917673;