rs1131896

Positions:

• chr6-31411338-G-A
• chr6-31411338-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001177519.3(MICA):​c.592G>A​(p.Gly198Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,574,762 control chromosomes in the GnomAD database, including 56,900 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6064 hom., cov: 31)
  • Exomes 𝑓: 0.26 (50836 hom.)
• Consequence: MICA NM_001177519.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.351139E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICA	NM_001177519.3	c.592G>A	p.Gly198Ser	missense_variant	3/6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.301G>A	p.Gly101Ser	missense_variant	3/6		NP_001276081.1
MICA	NM_001289153.2	c.301G>A	p.Gly101Ser	missense_variant	3/6		NP_001276082.1
MICA	NM_001289154.2	c.178G>A	p.Gly60Ser	missense_variant	3/6		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.592G>A	p.Gly198Ser	missense_variant	3/6	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41020 AN: 151394 Hom.: 6060 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.349

GnomAD3 exomes AF: 0.291 AC: 55418 AN: 190540 Hom.: 8865 AF XY: 0.296 AC XY: 30160 AN XY: 101918

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.389

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.257 AC: 366463 AN: 1423250 Hom.: 50836 Cov.: 37 AF XY: 0.261 AC XY: 184218 AN XY: 704546

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.425

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.271 AC: 41041 AN: 151512 Hom.: 6064 Cov.: 31 AF XY: 0.275 AC XY: 20339 AN XY: 74062

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.347

Alfa AF: 0.270 Hom.: 9532

Bravo AF: 0.283

TwinsUK AF: 0.227 AC: 842

ALSPAC AF: 0.233 AC: 899

ESP6500AA AF: 0.274 AC: 379

ESP6500EA AF: 0.253 AC: 805

ExAC AF: 0.259 AC: 30509

Asia WGS AF: 0.359 AC: 1249 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.46
DANN	Benign	0.76
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.013	N
MetaRNN	Benign	0.00044	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.4	.;D
REVEL	Benign	0.043
Sift	Benign	0.33	.;T
Sift4G	Benign	0.21	T;T
Polyphen		0.47	.;P
Vest4		0.067
MPC		0.12
ClinPred		0.047	T
GERP RS		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs1131896; hg19: chr6-31379115; COSMIC: COSV69826360;