6-31412384-G-GCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.641

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]

ACMG classification

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	UniProt
MICA	NM_001177519.3	c.952_953insCT	p.Gly318AlafsTer69	frameshift_variant	5/6	ENST00000449934.7
MICA	NM_001289152.2	c.661_662insCT	p.Gly221AlafsTer69	frameshift_variant	5/6
MICA	NM_001289153.2	c.661_662insCT	p.Gly221AlafsTer69	frameshift_variant	5/6
MICA	NM_001289154.2	c.538_539insCT	p.Gly180AlafsTer69	frameshift_variant	5/6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.267 AC: 32241 AN: 120766 Hom.: 4149 Cov.: 0

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.: 35 AF XY: 0.250 AC XY: 133865 AN XY: 534446

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.: 0 AF XY: 0.265 AC XY: 15567 AN XY: 58734

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

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41293539; hg19: chr6-31380161; COSMIC: COSV69826359;