rs1049390

Positions:

• chr11-2397107-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004356.4(CD81):​c.*241A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 564,704 control chromosomes in the GnomAD database, including 1,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (1198 hom., cov: 33)
  • Exomes 𝑓: 0.023 (469 hom.)
• Consequence: CD81 NM_004356.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0650

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-2397107-A-G is Benign according to our data. Variant chr11-2397107-A-G is described in ClinVar as [Benign]. Clinvar id is 1235271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD81	NM_004356.4	c.*241A>G		3_prime_UTR_variant	8/8	ENST00000263645.10	NP_004347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD81	ENST00000263645.10	c.*241A>G		3_prime_UTR_variant	8/8	1	NM_004356.4	ENSP00000263645	P1

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11373 AN: 151926 Hom.: 1185 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.0432

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.00696

Gnomad OTH AF: 0.0647

GnomAD4 exome AF: 0.0226 AC: 9346 AN: 412660 Hom.: 469 Cov.: 3 AF XY: 0.0234 AC XY: 5074 AN XY: 217192

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.0308

Gnomad4 ASJ exome AF: 0.0408

Gnomad4 EAS exome AF: 0.0264

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.000746

Gnomad4 NFE exome AF: 0.00742

Gnomad4 OTH exome AF: 0.0361

GnomAD4 genome AF: 0.0752 AC: 11433 AN: 152044 Hom.: 1198 Cov.: 33 AF XY: 0.0732 AC XY: 5445 AN XY: 74338

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.0219

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00696

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0466 Hom.: 110

Bravo AF: 0.0857

Asia WGS AF: 0.0540 AC: 186 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs1049390; hg19: chr11-2418337;