13-48307018-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000321.3(RB1):c.138-262G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,074 control chromosomes in the GnomAD database, including 28,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (28469 hom., cov: 33)
• Consequence: RB1 NM_000321.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0900

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 13-48307018-G-C is Benign according to our data. Variant chr13-48307018-G-C is described in ClinVar as [Benign]. Clinvar id is 1244896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RB1	NM_000321.3	c.138-262G>C		intron_variant		ENST00000267163.6
RB1	NM_001407165.1	c.138-262G>C		intron_variant
RB1	NM_001407166.1	c.138-262G>C		intron_variant
RB1	NM_001407167.1	c.138-262G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RB1	ENST00000267163.6	c.138-262G>C		intron_variant		1	NM_000321.3	P1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85755 AN: 151956 Hom.: 28474 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.564 AC: 85753 AN: 152074 Hom.: 28469 Cov.: 33 AF XY: 0.566 AC XY: 42082 AN XY: 74348

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.606

Alfa AF: 0.499 Hom.: 1666

Bravo AF: 0.547

Asia WGS AF: 0.536 AC: 1864 AN: 3468

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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.7
Dann	Benign	0.50

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: rs1981434; hg19: chr13-48881154;