11-2377598-T-G

Variant names:

• chr11-2377598-T-G
• rs1046814935
• NM_004356.4:c.49T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004356.4(CD81):​c.49T>G​(p.Phe17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,392,640 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F17L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CD81 NM_004356.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.49T>G	p.Phe17Val	missense	Exon 1 of 8	NP_004347.1	P60033
	CD81	NM_001425135.1		c.49T>G	p.Phe17Val	missense	Exon 1 of 8	NP_001412064.1
	CD81	NM_001425137.1		c.49T>G	p.Phe17Val	missense	Exon 1 of 8	NP_001412066.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD81	ENST00000263645.10	TSL:1 MANE Select	c.49T>G	p.Phe17Val	missense	Exon 1 of 8	ENSP00000263645.5	P60033
	CD81-AS1	ENST00000427151.1	TSL:1	n.392A>C		non_coding_transcript_exon	Exon 1 of 3
	CD81	ENST00000905044.1		c.49T>G	p.Phe17Val	missense	Exon 4 of 11	ENSP00000575103.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1392640 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 691232

African (AFR) AF: 0.00 AC: 0 AN: 29264

American (AMR) AF: 0.00 AC: 0 AN: 38934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24004

East Asian (EAS) AF: 0.00 AC: 0 AN: 34156

South Asian (SAS) AF: 0.00 AC: 0 AN: 80186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5406

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1074924

Other (OTH) AF: 0.00 AC: 0 AN: 56580

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	-0.0032
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	-0.032	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.3
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.44
Sift	Benign	0.046	D
Sift4G	Uncertain	0.030	D
Polyphen		0.48	P
Vest4		0.39
MutPred		0.75		Loss of stability (P = 0.1455)
MVP		0.87
MPC		1.3
ClinPred		0.97	D
GERP RS		1.1
PromoterAI		0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.63
gMVP		0.64
Mutation Taster		=48/52	disease causing

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: rs1046814935; hg19: chr11-2398828;