6-31412384-G-GCTGCTGCTGCT

Variant summary

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

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
• 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-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/exons	MANE	UniProt
MICA	NM_001177519.3	c.952_953insCTGCTGCTGCT	p.Gly318AlafsTer72	frameshift_variant	5/6	ENST00000449934.7
MICA	NM_001289152.2	c.661_662insCTGCTGCTGCT	p.Gly221AlafsTer72	frameshift_variant	5/6
MICA	NM_001289153.2	c.661_662insCTGCTGCTGCT	p.Gly221AlafsTer72	frameshift_variant	5/6
MICA	NM_001289154.2	c.538_539insCTGCTGCTGCT	p.Gly180AlafsTer72	frameshift_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICA	ENST00000449934.7	c.952_953insCTGCTGCTGCT	p.Gly318AlafsTer72	frameshift_variant	5/6	1	NM_001177519.3	P1
MICA	ENST00000421350.1	c.625_626insCTGCTGCTGCT	p.Gly209AlafsTer72	frameshift_variant	4/5	5
MICA	ENST00000616296.4	c.661_662insCTGCTGCTGCT	p.Gly221AlafsTer72	frameshift_variant	5/6	5
MICA	ENST00000674069.1	c.538_539insCTGCTGCTGCT	p.Gly180AlafsTer72	frameshift_variant	5/6

Frequencies

GnomAD3 genomes AF: 0.277 AC: 33466 AN: 120772 Hom.: 4510 Cov.: 0

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.: 35 AF XY: 0.199 AC XY: 105189 AN XY: 529734

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.: 0 AF XY: 0.285 AC XY: 16714 AN XY: 58708

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

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

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: COSV69826307;