rs67841474

Variant names:

• chr6-31412383-TG-T
• rs67841474
• NM_001177519.3:c.953delG

Your query was ambiguous. Multiple possible variants found:

• chr6-31412383-TG-T
• chr6-31412383-TG-TGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001177519.3(MICA):​c.953delG​(p.Gly318AlafsTer68) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,256,808 control chromosomes in the GnomAD database, including 14,129 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.20 (1348 hom., cov: 26)
  • Exomes 𝑓: 0.14 (12781 hom.)
• Consequence: MICA NM_001177519.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659
• Publications: 20 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177519.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	NM_001177519.3	MANE Select	c.953delG	p.Gly318AlafsTer68	frameshift	Exon 5 of 6	NP_001170990.1	Q96QC4
	MICA	NM_001289152.2		c.662delG	p.Gly221AlafsTer68	frameshift	Exon 5 of 6	NP_001276081.1	A0A024RCL3
	MICA	NM_001289153.2		c.662delG	p.Gly221AlafsTer68	frameshift	Exon 5 of 6	NP_001276082.1	A0A024RCL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	ENST00000449934.7	TSL:1 MANE Select	c.953delG	p.Gly318AlafsTer68	frameshift	Exon 5 of 6	ENSP00000413079.1	Q96QC4
	MICA	ENST00000892120.1		c.698delG	p.Gly233AlafsTer68	frameshift	Exon 4 of 5	ENSP00000562179.1
	MICA	ENST00000616296.4	TSL:5	c.662delG	p.Gly221AlafsTer68	frameshift	Exon 5 of 6	ENSP00000482382.1	A0A024RCL3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 16232 AN: 83068 Hom.: 1342 Cov.: 26

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.212 AC: 29748 AN: 140244 AF XY: 0.210

Gnomad AFR exome AF: 0.0488

Gnomad AMR exome AF: 0.346

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.395

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.142 AC: 166973 AN: 1173710 Hom.: 12781 Cov.: 35 AF XY: 0.145 AC XY: 84310 AN XY: 581660

African (AFR) AF: 0.0271 AC: 754 AN: 27784

American (AMR) AF: 0.237 AC: 7868 AN: 33180

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 3794 AN: 22102

East Asian (EAS) AF: 0.380 AC: 11875 AN: 31270

South Asian (SAS) AF: 0.211 AC: 15317 AN: 72762

European-Finnish (FIN) AF: 0.208 AC: 8366 AN: 40234

Middle Eastern (MID) AF: 0.155 AC: 732 AN: 4708

European-Non Finnish (NFE) AF: 0.124 AC: 110763 AN: 892708

Other (OTH) AF: 0.153 AC: 7504 AN: 48962

GnomAD4 genome AF: 0.195 AC: 16239 AN: 83098 Hom.: 1348 Cov.: 26 AF XY: 0.209 AC XY: 8460 AN XY: 40476

African (AFR) AF: 0.0745 AC: 1163 AN: 15614

American (AMR) AF: 0.329 AC: 2604 AN: 7912

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 504 AN: 1616

East Asian (EAS) AF: 0.489 AC: 1768 AN: 3612

South Asian (SAS) AF: 0.377 AC: 1023 AN: 2710

European-Finnish (FIN) AF: 0.246 AC: 1597 AN: 6504

Middle Eastern (MID) AF: 0.314 AC: 37 AN: 118

European-Non Finnish (NFE) AF: 0.167 AC: 7270 AN: 43474

Other (OTH) AF: 0.228 AC: 239 AN: 1046

Alfa AF: 0.0986 Hom.: 68

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.66
Mutation Taster		=192/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs67841474; hg19: chr6-31380160; COSMIC: COSV69826358;