rs4151540

Positions:

• chr13-48381523-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001407166.1(RB1):​c.*69_*70insAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,281,506 control chromosomes in the GnomAD database, including 45,161 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4251 hom., cov: 24)
  • Exomes 𝑓: 0.26 (40910 hom.)
• Consequence: RB1 NM_001407166.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0210

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 -10 ACMG points.

• BP6: Variant 13-48381523-C-CAA is Benign according to our data. Variant chr13-48381523-C-CAA is described in ClinVar as [Benign]. Clinvar id is 1225861.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RB1	NM_000321.3	c.1695+81_1695+82insAA		intron_variant		ENST00000267163.6	NP_000312.2
RB1	NM_001407166.1	c.*69_*70insAA		3_prime_UTR_variant	17/17		NP_001394095.1
RB1	NM_001407165.1	c.1695+81_1695+82insAA		intron_variant			NP_001394094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.1695+81_1695+82insAA		intron_variant		1	NM_000321.3	ENSP00000267163.4
RB1	ENST00000650461.1	c.1695+81_1695+82insAA		intron_variant				ENSP00000497193.1
RB1	ENST00000643064.1	c.192+81_192+82insAA		intron_variant				ENSP00000496005.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35087 AN: 151906 Hom.: 4257 Cov.: 24

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.261 AC: 295159 AN: 1129482 Hom.: 40910 AF XY: 0.261 AC XY: 149955 AN XY: 573572

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.231 AC: 35082 AN: 152024 Hom.: 4251 Cov.: 24 AF XY: 0.234 AC XY: 17374 AN XY: 74300

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.214

Alfa AF: 0.252 Hom.: 516

Bravo AF: 0.225

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4151540; hg19: chr13-48955659;