rs1049390

Variant names:

• chr11-2397107-A-G
• rs1049390
• ENST00000531840.1:n.4946A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000531840.1(CD81):​n.4946A>G variant causes a non coding transcript exon 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 ENST00000531840.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0650
• Publications: 5 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: AR, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CD81	NM_004356.4	c.*241A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000263645.10	NP_004347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD81	ENST00000263645.10	c.*241A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_004356.4	ENSP00000263645.5

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

African (AFR) AF: 0.231 AC: 2662 AN: 11530

American (AMR) AF: 0.0308 AC: 570 AN: 18510

Ashkenazi Jewish (ASJ) AF: 0.0408 AC: 522 AN: 12796

East Asian (EAS) AF: 0.0264 AC: 741 AN: 28060

South Asian (SAS) AF: 0.0458 AC: 2068 AN: 45186

European-Finnish (FIN) AF: 0.000746 AC: 19 AN: 25484

Middle Eastern (MID) AF: 0.0496 AC: 89 AN: 1796

European-Non Finnish (NFE) AF: 0.00742 AC: 1824 AN: 245694

Other (OTH) AF: 0.0361 AC: 851 AN: 23604

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

African (AFR) AF: 0.234 AC: 9670 AN: 41406

American (AMR) AF: 0.0415 AC: 634 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3470

East Asian (EAS) AF: 0.0219 AC: 113 AN: 5160

South Asian (SAS) AF: 0.0435 AC: 209 AN: 4806

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10616

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.00696 AC: 473 AN: 67992

Other (OTH) AF: 0.0687 AC: 145 AN: 2110

Alfa AF: 0.0497 Hom.: 183

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		0.065
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: rs1049390; hg19: chr11-2418337;