chr6-31412384-G-GCT

Variant names:

• chr6-31412384-G-GCT
• rs41293539
• NM_001177519.3:c.952_953insCT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

ENSG00000288587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.952_953insCT	p.Gly318AlafsTer69	frameshift_variant	Exon 5 of 6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.661_662insCT	p.Gly221AlafsTer69	frameshift_variant	Exon 5 of 6		NP_001276081.1
MICA	NM_001289153.2	c.661_662insCT	p.Gly221AlafsTer69	frameshift_variant	Exon 5 of 6		NP_001276082.1
MICA	NM_001289154.2	c.538_539insCT	p.Gly180AlafsTer69	frameshift_variant	Exon 5 of 6		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.952_953insCT	p.Gly318AlafsTer69	frameshift_variant	Exon 5 of 6	1	NM_001177519.3	ENSP00000413079.1

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

African (AFR) AF: 0.306 AC: 9240 AN: 30180

American (AMR) AF: 0.282 AC: 8455 AN: 29978

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 8430 AN: 21762

East Asian (EAS) AF: 0.334 AC: 7851 AN: 23478

South Asian (SAS) AF: 0.346 AC: 22814 AN: 65950

European-Finnish (FIN) AF: 0.127 AC: 4303 AN: 33760

Middle Eastern (MID) AF: 0.508 AC: 2451 AN: 4828

European-Non Finnish (NFE) AF: 0.231 AC: 189752 AN: 822778

Other (OTH) AF: 0.270 AC: 12344 AN: 45642

GnomAD4 genome AF: 0.267 AC: 32266 AN: 120850 Hom.: 4156 Cov.: 0 AF XY: 0.265 AC XY: 15567 AN XY: 58734

African (AFR) AF: 0.298 AC: 11282 AN: 37918

American (AMR) AF: 0.316 AC: 3921 AN: 12414

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1142 AN: 3032

East Asian (EAS) AF: 0.220 AC: 624 AN: 2838

South Asian (SAS) AF: 0.352 AC: 1345 AN: 3822

European-Finnish (FIN) AF: 0.118 AC: 847 AN: 7206

Middle Eastern (MID) AF: 0.398 AC: 94 AN: 236

European-Non Finnish (NFE) AF: 0.242 AC: 12309 AN: 50888

Other (OTH) AF: 0.369 AC: 633 AN: 1716

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-0.64
Mutation Taster		=183/17	polymorphism

Splicing

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

Other links and lift over

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