Variant 6-31412384-G-GCTGCTGCTGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001177519.3(MICA):c.952_953insCTGCTGCTGCT(p.Gly318AlafsTer72) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.28 ( 4518 hom., cov: 0)

Exomes 𝑓: 0.20 ( 19456 hom. )

Failed GnomAD Quality Control

Consequence

MICA
NM_001177519.3 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.641

Variant links:

Genes affected

MICA (HGNC:7090): (MHC class I polypeptide-related sequence A) This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]

MICA links:

ENSG00000288587 (HGNC:):

ENSG00000288587 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-31412384-G-GCTGCTGCTGCT is Benign according to our data. Variant chr6-31412384-G-GCTGCTGCTGCT is described in ClinVar as [Benign]. Clinvar id is 403088.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3 link	c.952_953insCTGCTGCTGCT	p.Gly318AlafsTer72	frameshift_variant	Exon 5 of 6	ENST00000449934.7	NP_001170990.1	Q96QC4
MICA	NM_001289152.2 link	c.661_662insCTGCTGCTGCT	p.Gly221AlafsTer72	frameshift_variant	Exon 5 of 6		NP_001276081.1	Q96QC4A0A024RCL3
MICA	NM_001289153.2 link	c.661_662insCTGCTGCTGCT	p.Gly221AlafsTer72	frameshift_variant	Exon 5 of 6		NP_001276082.1	Q96QC4A0A024RCL3
MICA	NM_001289154.2 link	c.538_539insCTGCTGCTGCT	p.Gly180AlafsTer72	frameshift_variant	Exon 5 of 6		NP_001276083.1	Q96QC4A0A0G2JJ55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7 link	c.952_953insCTGCTGCTGCT	p.Gly318AlafsTer72	frameshift_variant	Exon 5 of 6	1	NM_001177519.3	ENSP00000413079.1		Q96QC4

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

33466

AN:

120772

Hom.:

4510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.270

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.252

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.198

AC:

211320

AN:

1069922

Hom.:

19456

Cov.:

AF XY:

0.199

AC XY:

105189

AN XY:

529734

show subpopulations

Gnomad4 AFR exome

AF:

0.367

Gnomad4 AMR exome

AF:

0.388

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.308

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.277

AC:

33509

AN:

120856

Hom.:

4518

Cov.:

AF XY:

0.285

AC XY:

16714

AN XY:

58708

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.315

Gnomad4 EAS

AF:

0.315

Gnomad4 SAS

AF:

0.286

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.252

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Not present in FAST (frequency). ExAC: 23.9% (9166/38406) total chromosomes -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over