11-2390306-C-T

Variant names:

• chr11-2390306-C-T
• rs12291676
• NM_004356.4:c.67-106C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0860
• Publications: 2 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 -20 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 VariationId is 1244889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

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.67-106C>T		intron	N/A	NP_004347.1	P60033
	CD81	NM_001425135.1		c.67-106C>T		intron	N/A	NP_001412064.1
	CD81	NM_001425137.1		c.67-106C>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.67-106C>T		intron	N/A	ENSP00000263645.5	P60033
	CD81	ENST00000533417.6	TSL:3	c.268-106C>T		intron	N/A	ENSP00000435633.2	H0YEE2
	CD81	ENST00000381036.7	TSL:3	c.181-106C>T		intron	N/A	ENSP00000370424.3	A6NMH8

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

African (AFR) AF: 0.340 AC: 6699 AN: 19728

American (AMR) AF: 0.0347 AC: 1513 AN: 43546

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 916 AN: 21590

East Asian (EAS) AF: 0.0266 AC: 969 AN: 36474

South Asian (SAS) AF: 0.0449 AC: 3210 AN: 71480

European-Finnish (FIN) AF: 0.000678 AC: 28 AN: 41324

Middle Eastern (MID) AF: 0.0575 AC: 162 AN: 2818

European-Non Finnish (NFE) AF: 0.00782 AC: 3570 AN: 456430

Other (OTH) AF: 0.0435 AC: 1590 AN: 36540

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

African (AFR) AF: 0.336 AC: 13950 AN: 41464

American (AMR) AF: 0.0534 AC: 816 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.0214 AC: 110 AN: 5132

South Asian (SAS) AF: 0.0446 AC: 215 AN: 4826

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10620

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.00766 AC: 521 AN: 68032

Other (OTH) AF: 0.0893 AC: 189 AN: 2116

Alfa AF: 0.0737 Hom.: 210

Bravo AF: 0.119

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.69
PhyloP100		-0.086
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs12291676; hg19: chr11-2411536;