11-2390397-C-T

Variant names:

• chr11-2390397-C-T
• rs551192381
• NM_004356.4:c.67-15C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004356.4(CD81):​c.67-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,601,728 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (14 hom.)
• Consequence: CD81 NM_004356.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.286
• Publications: 0 publications found

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]

CD81 Gene-Disease associations (from GenCC):

• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency, common variable, 6

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-2390397-C-T is Benign according to our data. Variant chr11-2390397-C-T is described in ClinVar as Benign. ClinVar VariationId is 1164238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR,AD,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004356.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD81	NM_004356.4	MANE Select	c.67-15C>T		intron	N/A	NP_004347.1	P60033
	CD81	NM_001425135.1		c.67-15C>T		intron	N/A	NP_001412064.1
	CD81	NM_001425137.1		c.67-15C>T		intron	N/A	NP_001412066.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD81	ENST00000263645.10	TSL:1 MANE Select	c.67-15C>T		intron	N/A	ENSP00000263645.5	P60033
	CD81	ENST00000533417.6	TSL:3	c.268-15C>T		intron	N/A	ENSP00000435633.2	H0YEE2
	CD81	ENST00000381036.7	TSL:3	c.181-15C>T		intron	N/A	ENSP00000370424.3	A6NMH8

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152210 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00152 AC: 380 AN: 249732 AF XY: 0.00184

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.000742 AC: 1076 AN: 1449400 Hom.: 14 Cov.: 28 AF XY: 0.00101 AC XY: 726 AN XY: 721848

African (AFR) AF: 0.0000602 AC: 2 AN: 33246

American (AMR) AF: 0.000268 AC: 12 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39642

South Asian (SAS) AF: 0.0109 AC: 942 AN: 86062

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 51974

Middle Eastern (MID) AF: 0.000355 AC: 2 AN: 5636

European-Non Finnish (NFE) AF: 0.0000417 AC: 46 AN: 1102092

Other (OTH) AF: 0.00115 AC: 69 AN: 59964

GnomAD4 genome AF: 0.000505 AC: 77 AN: 152328 Hom.: 1 Cov.: 33 AF XY: 0.000698 AC XY: 52 AN XY: 74486

African (AFR) AF: 0.0000962 AC: 4 AN: 41572

American (AMR) AF: 0.000196 AC: 3 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.0130 AC: 63 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000384 Hom.: 0

Bravo AF: 0.000159

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.3
DANN	Benign	0.80
PhyloP100		0.29
PromoterAI		0.30	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs551192381; hg19: chr11-2411627;