11-836092-A-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_004357.5(CD151):c.23A>C(p.Lys8Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000525 in 1,612,762 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00054 (9 hom.)
• Consequence: CD151 NM_004357.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.01

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037566423).
• BP6: Variant 11-836092-A-C is Benign according to our data. Variant chr11-836092-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 750620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 2 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD151	NM_004357.5	c.23A>C	p.Lys8Thr	missense_variant	3/9	ENST00000397420.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD151	ENST00000397420.9	c.23A>C	p.Lys8Thr	missense_variant	3/9	1	NM_004357.5	P3

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152222 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00103 AC: 258 AN: 250084 Hom.: 2 AF XY: 0.00144 AC XY: 196 AN XY: 135670

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00788

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000544 AC: 795 AN: 1460422 Hom.: 9 Cov.: 33 AF XY: 0.000758 AC XY: 551 AN XY: 726550

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00791

Gnomad4 FIN exome AF: 0.0000954

Gnomad4 NFE exome AF: 0.0000585

Gnomad4 OTH exome AF: 0.000596

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152340 Hom.: 0 Cov.: 34 AF XY: 0.000470 AC XY: 35 AN XY: 74490

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000151 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00118 AC: 143

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	CD151: BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

CD151-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.;T;T;T;.;T;.;.;T;.;T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.58
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.0038	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L;.;L;L;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	0.65	N;N;N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.056
Sift	Benign	0.088	T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0050	B;.;B;B;.;.;.;.;.;.;.;.;.
Vest4		0.20
MVP		0.33
MPC		0.17
ClinPred		0.036	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.15
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199816860; hg19: chr11-836092;