chr11-2390306-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004356.4(CD81):​c.67-106C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 729,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD81 NM_004356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 1 AN: 729994 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 390900

African (AFR) AF: 0.00 AC: 0 AN: 19746

American (AMR) AF: 0.00 AC: 0 AN: 43550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21596

East Asian (EAS) AF: 0.0000274 AC: 1 AN: 36476

South Asian (SAS) AF: 0.00 AC: 0 AN: 71482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2820

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 456458

Other (OTH) AF: 0.00 AC: 0 AN: 36542

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.71
PhyloP100		-0.086
PromoterAI		0.0021	Neutral

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;