11-2390138-G-A

Position:

• chr11-2390138-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000263645.10(CD81):​c.67-274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 573,140 control chromosomes in the GnomAD database, including 3,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2417 hom., cov: 33)
  • Exomes 𝑓: 0.027 (866 hom.)
• Consequence: CD81 ENST00000263645.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.520

Genes affected

CD81 (HGNC:1701): (CD81 molecule) 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. This protein appears to promote muscle cell fusion and support myotube maintenance. Also it may be involved in signal transduction. This gene is localized in the tumor-suppressor gene region and thus it is a candidate gene for malignancies. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-2390138-G-A is Benign according to our data. Variant chr11-2390138-G-A is described in ClinVar as [Benign]. Clinvar id is 1237143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD81	NM_004356.4	c.67-274G>A		intron_variant		ENST00000263645.10	NP_004347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD81	ENST00000263645.10	c.67-274G>A		intron_variant		1	NM_004356.4	ENSP00000263645	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15973 AN: 151998 Hom.: 2403 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.0219

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.00764

Gnomad OTH AF: 0.0881

GnomAD4 exome AF: 0.0273 AC: 11510 AN: 421024 Hom.: 866 Cov.: 0 AF XY: 0.0274 AC XY: 6072 AN XY: 221922

Gnomad4 AFR exome AF: 0.337

Gnomad4 AMR exome AF: 0.0403

Gnomad4 ASJ exome AF: 0.0417

Gnomad4 EAS exome AF: 0.0274

Gnomad4 SAS exome AF: 0.0462

Gnomad4 FIN exome AF: 0.000863

Gnomad4 NFE exome AF: 0.00822

Gnomad4 OTH exome AF: 0.0457

GnomAD4 genome AF: 0.105 AC: 16030 AN: 152116 Hom.: 2417 Cov.: 33 AF XY: 0.102 AC XY: 7581 AN XY: 74372

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.0536

Gnomad4 ASJ AF: 0.0450

Gnomad4 EAS AF: 0.0219

Gnomad4 SAS AF: 0.0441

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00763

Gnomad4 OTH AF: 0.0896

Alfa AF: 0.0401 Hom.: 547

Bravo AF: 0.119

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.63

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: rs12278063; hg19: chr11-2411368;