13-48381238-C-T

Position:

• chr13-48381238-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_000321.3(RB1):​c.1499-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RB1 NM_000321.3 intron
• Scores: Splicing: ADA: 0.0009395
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.242

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 13-48381238-C-T is Benign according to our data. Variant chr13-48381238-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 458128.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RB1	NM_000321.3	c.1499-9C>T		intron_variant		ENST00000267163.6	NP_000312.2
RB1	NM_001407165.1	c.1499-9C>T		intron_variant			NP_001394094.1
RB1	NM_001407166.1	c.1499-9C>T		intron_variant			NP_001394095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.1499-9C>T		intron_variant		1	NM_000321.3	ENSP00000267163.4
RB1	ENST00000650461.1	c.1499-9C>T		intron_variant				ENSP00000497193.1
RB1	ENST00000643064.1	c.-14C>T		upstream_gene_variant				ENSP00000496005.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 13 AN: 149138 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000729

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000744

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00251 AC: 525 AN: 209028 Hom.: 0 AF XY: 0.00236 AC XY: 268 AN XY: 113328

Gnomad AFR exome AF: 0.00345

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00359

Gnomad EAS exome AF: 0.00160

Gnomad SAS exome AF: 0.00161

Gnomad FIN exome AF: 0.00234

Gnomad NFE exome AF: 0.00302

Gnomad OTH exome AF: 0.00320

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000412 AC: 585 AN: 1421168 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 284 AN XY: 705586

Gnomad4 AFR exome AF: 0.00167

Gnomad4 AMR exome AF: 0.00275

Gnomad4 ASJ exome AF: 0.00133

Gnomad4 EAS exome AF: 0.000180

Gnomad4 SAS exome AF: 0.000658

Gnomad4 FIN exome AF: 0.0000957

Gnomad4 NFE exome AF: 0.000251

Gnomad4 OTH exome AF: 0.000909

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000871 AC: 13 AN: 149254 Hom.: 0 Cov.: 32 AF XY: 0.0000550 AC XY: 4 AN XY: 72728

Gnomad4 AFR AF: 0.0000245

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000729

Gnomad4 NFE AF: 0.0000745

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00421 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinoblastoma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 29, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00094
dbscSNV1_RF	Benign	0.096
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: rs201020747; hg19: chr13-48955374; COSMIC: COSV105078135; COSMIC: COSV105078135;