13-48303764-G-C

Variant names:

• chr13-48303764-G-C
• rs1014776340
• NM_000321.3:c.-149G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000321.3(RB1):​c.-149G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,490 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: RB1 NM_000321.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16
• Publications: 0 publications found

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]

RB1-DT (HGNC:42778): (RB1 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RB1	NM_000321.3	MANE Select	c.-149G>C		5_prime_UTR	Exon 1 of 27	NP_000312.2	P06400
	RB1	NM_001407165.1		c.-149G>C		5_prime_UTR	Exon 1 of 27	NP_001394094.1	A0A3B3IS71
	RB1	NM_001407166.1		c.-149G>C		5_prime_UTR	Exon 1 of 17	NP_001394095.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RB1	ENST00000267163.6	TSL:1 MANE Select	c.-149G>C		5_prime_UTR	Exon 1 of 27	ENSP00000267163.4	P06400
	RB1	ENST00000924352.1		c.-149G>C		5_prime_UTR	Exon 1 of 28	ENSP00000594411.1
	RB1	ENST00000650461.1		c.-149G>C		5_prime_UTR	Exon 1 of 27	ENSP00000497193.1	A0A3B3IS71

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096490 Hom.: 0 Cov.: 15 AF XY: 0.00000185 AC XY: 1 AN XY: 540340

African (AFR) AF: 0.00 AC: 0 AN: 21696

American (AMR) AF: 0.00 AC: 0 AN: 17578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19572

East Asian (EAS) AF: 0.00 AC: 0 AN: 26660

South Asian (SAS) AF: 0.00 AC: 0 AN: 62360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3348

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 867218

Other (OTH) AF: 0.0000214 AC: 1 AN: 46722

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.96
PhyloP100		2.2
PromoterAI		-0.28	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1014776340; hg19: chr13-48877900;