rs1130663

Positions:

• chr11-837582-G-A
• chr11-837582-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004357.5(CD151):​c.579G>A​(p.Gly193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,612,376 control chromosomes in the GnomAD database, including 379,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33089 hom., cov: 34)
  • Exomes 𝑓: 0.68 (346811 hom.)
• Consequence: CD151 NM_004357.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0920

Genes affected

CD151 (HGNC:1630): (CD151 molecule (Raph blood group)) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins and other transmembrane 4 superfamily proteins. It is involved in cellular processes including cell adhesion and may regulate integrin trafficking and/or function. This protein enhances cell motility, invasion and metastasis of cancer cells. Multiple alternatively spliced transcript variants that encode the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

POLR2L (HGNC:9199): (RNA polymerase II, I and III subunit L) This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-837582-G-A is Benign according to our data. Variant chr11-837582-G-A is described in ClinVar as [Benign]. Clinvar id is 1277016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-837582-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.092 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD151	NM_004357.5	c.579G>A	p.Gly193=	synonymous_variant	7/9	ENST00000397420.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD151	ENST00000397420.9	c.579G>A	p.Gly193=	synonymous_variant	7/9	1	NM_004357.5	P3

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99089 AN: 151874 Hom.: 33077 Cov.: 34

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.623

GnomAD3 exomes AF: 0.681 AC: 170009 AN: 249696 Hom.: 59785 AF XY: 0.666 AC XY: 90165 AN XY: 135422

Gnomad AFR exome AF: 0.541

Gnomad AMR exome AF: 0.819

Gnomad ASJ exome AF: 0.488

Gnomad EAS exome AF: 0.861

Gnomad SAS exome AF: 0.483

Gnomad FIN exome AF: 0.757

Gnomad NFE exome AF: 0.686

Gnomad OTH exome AF: 0.667

GnomAD4 exome AF: 0.684 AC: 999333 AN: 1460384 Hom.: 346811 Cov.: 53 AF XY: 0.677 AC XY: 491826 AN XY: 726500

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.811

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.888

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.752

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.655

GnomAD4 genome AF: 0.652 AC: 99129 AN: 151992 Hom.: 33089 Cov.: 34 AF XY: 0.652 AC XY: 48462 AN XY: 74306

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.625

Alfa AF: 0.667 Hom.: 41530

Bravo AF: 0.651

Asia WGS AF: 0.682 AC: 2370 AN: 3478

EpiCase AF: 0.663

EpiControl AF: 0.665

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1130663; hg19: chr11-837582;