rs148992508

Positions:

• chr13-48360037-G-A
• chr13-48360037-G-C
• chr13-48360037-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000321.3(RB1):​c.628G>A​(p.Asp210Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RB1 NM_000321.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.18

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RB1	NM_000321.3	c.628G>A	p.Asp210Asn	missense_variant	7/27	ENST00000267163.6	NP_000312.2
RB1	NM_001407165.1	c.628G>A	p.Asp210Asn	missense_variant	7/27		NP_001394094.1
RB1	NM_001407166.1	c.628G>A	p.Asp210Asn	missense_variant	7/17		NP_001394095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.628G>A	p.Asp210Asn	missense_variant	7/27	1	NM_000321.3	ENSP00000267163	P1
RB1	ENST00000467505.5	c.158G>A	p.Arg53Lys	missense_variant, NMD_transcript_variant	2/3	1		ENSP00000434702
RB1	ENST00000650461.1	c.628G>A	p.Asp210Asn	missense_variant	7/27			ENSP00000497193
RB1	ENST00000525036.1	n.790G>A		non_coding_transcript_exon_variant	7/7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Benign	0.94
DEOGEN2	Pathogenic	0.82	D;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Uncertain	0.45
Sift	Uncertain	0.0070	D;.
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.67
MutPred		0.46		Gain of catalytic residue at V213 (P = 0);Gain of catalytic residue at V213 (P = 0);
MVP		0.84
MPC		0.50
ClinPred		0.89	D
GERP RS		5.6
Varity_R		0.51
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-48934173;