11-835878-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004357.5(CD151):c.-7-185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 571,142 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (20 hom., cov: 33)
  • Exomes 𝑓: 0.016 (83 hom.)
• Consequence: CD151 NM_004357.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.774

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 11-835878-G-A is Benign according to our data. Variant chr11-835878-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1179338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0128 (1944/152080) while in subpopulation NFE AF= 0.0164 (1116/67998). AF 95% confidence interval is 0.0156. There are 20 homozygotes in gnomad4. There are 997 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD151	NM_004357.5	c.-7-185G>A		intron_variant		ENST00000397420.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD151	ENST00000397420.9	c.-7-185G>A		intron_variant		1	NM_004357.5	P3

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1945 AN: 151960 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.0158 AC: 6623 AN: 419062 Hom.: 83 Cov.: 2 AF XY: 0.0162 AC XY: 3573 AN XY: 221220

Gnomad4 AFR exome AF: 0.00339

Gnomad4 AMR exome AF: 0.00558

Gnomad4 ASJ exome AF: 0.0526

Gnomad4 EAS exome AF: 0.0000356

Gnomad4 SAS exome AF: 0.0174

Gnomad4 FIN exome AF: 0.0253

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0171

GnomAD4 genome AF: 0.0128 AC: 1944 AN: 152080 Hom.: 20 Cov.: 33 AF XY: 0.0134 AC XY: 997 AN XY: 74330

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.0570

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0310

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0139 Hom.: 1

Bravo AF: 0.0108

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 07, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.67
Dann	Benign	0.75

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: rs34037130; hg19: chr11-835878;