11-2390306-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004356.4(CD81):c.67-106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 882,090 control chromosomes in the GnomAD database, including 3,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (2406 hom., cov: 33)
  • Exomes 𝑓: 0.026 (1430 hom.)
• Consequence: CD81 NM_004356.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0860

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-2390306-C-T is Benign according to our data. Variant chr11-2390306-C-T is described in ClinVar as [Benign]. Clinvar id is 1244889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD81	NM_004356.4	c.67-106C>T		intron_variant		ENST00000263645.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD81	ENST00000263645.10	c.67-106C>T		intron_variant		1	NM_004356.4	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15946 AN: 152040 Hom.: 2394 Cov.: 33

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.00767

Gnomad OTH AF: 0.0880

GnomAD4 exome AF: 0.0256 AC: 18657 AN: 729930 Hom.: 1430 Cov.: 10 AF XY: 0.0248 AC XY: 9688 AN XY: 390860

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.0347

Gnomad4 ASJ exome AF: 0.0424

Gnomad4 EAS exome AF: 0.0266

Gnomad4 SAS exome AF: 0.0449

Gnomad4 FIN exome AF: 0.000678

Gnomad4 NFE exome AF: 0.00782

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.105 AC: 16000 AN: 152160 Hom.: 2406 Cov.: 33 AF XY: 0.102 AC XY: 7567 AN XY: 74394

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.0534

Gnomad4 ASJ AF: 0.0449

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.0446

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00766

Gnomad4 OTH AF: 0.0893

Alfa AF: 0.0626 Hom.: 161

Bravo AF: 0.119

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.2
Dann	Benign	0.69

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: rs12291676; hg19: chr11-2411536;