11-2377586-C-T

Variant names:

• chr11-2377586-C-T
• rs776912412
• NM_004356.4:c.37C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001425130.1(CD81):​c.-173C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000389 in 1,540,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD81 NM_001425130.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.819
• 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-AS1 (HGNC:49384): (CD81 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 11-2377586-C-T is Benign according to our data. Variant chr11-2377586-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1602069.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001425130.1. 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.37C>T	p.Leu13Leu	synonymous	Exon 1 of 8	NP_004347.1	P60033
	CD81	NM_001425130.1		c.-173C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001412059.1	E9PJK1
	CD81	NM_001425135.1		c.37C>T	p.Leu13Leu	synonymous	Exon 1 of 8	NP_001412064.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD81	ENST00000263645.10	TSL:1 MANE Select	c.37C>T	p.Leu13Leu	synonymous	Exon 1 of 8	ENSP00000263645.5	P60033
	CD81-AS1	ENST00000427151.1	TSL:1	n.404G>A		splice_region non_coding_transcript_exon	Exon 1 of 3
	CD81	ENST00000905044.1		c.37C>T	p.Leu13Leu	synonymous	Exon 4 of 11	ENSP00000575103.1

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 151206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000511 AC: 1 AN: 195690 AF XY: 0.00000933

Gnomad AFR exome AF: 0.000103

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1389772 Hom.: 0 Cov.: 29 AF XY: 0.00000290 AC XY: 2 AN XY: 689678

African (AFR) AF: 0.0000687 AC: 2 AN: 29098

American (AMR) AF: 0.00 AC: 0 AN: 38534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23908

East Asian (EAS) AF: 0.00 AC: 0 AN: 33738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5332

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073848

Other (OTH) AF: 0.00 AC: 0 AN: 56364

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 151206 Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2 AN XY: 73838

African (AFR) AF: 0.0000969 AC: 4 AN: 41290

American (AMR) AF: 0.00 AC: 0 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67742

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000258 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Likely 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	-0.34
CADD	Benign	20
DANN	Uncertain	0.99
PhyloP100		0.82
PromoterAI		0.10	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs776912412; hg19: chr11-2398816;