Variant rs41293539 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_953insCT(p.Gly318AlafsTer69) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,199,206 control chromosomes in the GnomAD database, including 32,615 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.27 ( 4156 hom., cov: 0)

Exomes 𝑓: 0.25 ( 28459 hom. )

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-31412384-G-GCT is Benign according to our data. Variant chr6-31412384-G-GCT is described in ClinVar as [Benign]. Clinvar id is 403087.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MICA	NM_001177519.3 linkuse as main transcript	c.952_953insCT	p.Gly318AlafsTer69	frameshift_variant	5/6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2 linkuse as main transcript	c.661_662insCT	p.Gly221AlafsTer69	frameshift_variant	5/6		NP_001276081.1
MICA	NM_001289153.2 linkuse as main transcript	c.661_662insCT	p.Gly221AlafsTer69	frameshift_variant	5/6		NP_001276082.1
MICA	NM_001289154.2 linkuse as main transcript	c.538_539insCT	p.Gly180AlafsTer69	frameshift_variant	5/6		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MICA	ENST00000449934.7 linkuse as main transcript	c.952_953insCT	p.Gly318AlafsTer69	frameshift_variant	5/6	1	NM_001177519.3	ENSP00000413079	P1
MICA	ENST00000421350.1 linkuse as main transcript	c.625_626insCT	p.Gly209AlafsTer69	frameshift_variant	4/5	5		ENSP00000402410
MICA	ENST00000616296.4 linkuse as main transcript	c.661_662insCT	p.Gly221AlafsTer69	frameshift_variant	5/6	5		ENSP00000482382
MICA	ENST00000674069.1 linkuse as main transcript	c.538_539insCT	p.Gly180AlafsTer69	frameshift_variant	5/6			ENSP00000501157

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

32241

AN:

120766

Hom.:

4149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.0885

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.370

GnomAD4 exome

AF:

0.246

AC:

265640

AN:

1078356

Hom.:

28459

Cov.:

AF XY:

0.250

AC XY:

133865

AN XY:

534446

show subpopulations

Gnomad4 AFR exome

AF:

0.306

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.346

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.267

AC:

32266

AN:

120850

Hom.:

4156

Cov.:

AF XY:

0.265

AC XY:

15567

AN XY:

58734

show subpopulations

Gnomad4 AFR

AF:

0.298

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.377

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.352

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.369

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: MAF -

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