rs1051792

Variant names:

• chr6-31411200-G-A
• rs1051792
• NM_001177519.3:c.454G>A

Variant summary

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

The NM_001177519.3(MICA):​c.454G>A​(p.Val152Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,612,522 control chromosomes in the GnomAD database, including 74,084 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.35 (10105 hom., cov: 31)
  • Exomes 𝑓: 0.29 (63979 hom.)
• Consequence: MICA NM_001177519.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 83 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 (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.454G>A	p.Val152Met	missense_variant	Exon 3 of 6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.163G>A	p.Val55Met	missense_variant	Exon 3 of 6		NP_001276081.1
MICA	NM_001289153.2	c.163G>A	p.Val55Met	missense_variant	Exon 3 of 6		NP_001276082.1
MICA	NM_001289154.2	c.84-44G>A		intron_variant	Intron 2 of 5		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.454G>A	p.Val152Met	missense_variant	Exon 3 of 6	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53400 AN: 151504 Hom.: 10086 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.353

GnomAD2 exomes AF: 0.337 AC: 83619 AN: 248078 AF XY: 0.329

Gnomad AFR exome AF: 0.456

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.341

Gnomad FIN exome AF: 0.357

Gnomad NFE exome AF: 0.283

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.287 AC: 419302 AN: 1460900 Hom.: 63979 Cov.: 68 AF XY: 0.287 AC XY: 208884 AN XY: 726728

African (AFR) AF: 0.457 AC: 15283 AN: 33450

American (AMR) AF: 0.449 AC: 19852 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 11944 AN: 26124

East Asian (EAS) AF: 0.305 AC: 12113 AN: 39650

South Asian (SAS) AF: 0.301 AC: 25983 AN: 86182

European-Finnish (FIN) AF: 0.350 AC: 18689 AN: 53382

Middle Eastern (MID) AF: 0.299 AC: 1725 AN: 5766

European-Non Finnish (NFE) AF: 0.265 AC: 294895 AN: 1111760

Other (OTH) AF: 0.312 AC: 18818 AN: 60360

GnomAD4 genome AF: 0.353 AC: 53465 AN: 151622 Hom.: 10105 Cov.: 31 AF XY: 0.356 AC XY: 26407 AN XY: 74078

African (AFR) AF: 0.446 AC: 18398 AN: 41224

American (AMR) AF: 0.392 AC: 5954 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1622 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1632 AN: 5148

South Asian (SAS) AF: 0.307 AC: 1475 AN: 4806

European-Finnish (FIN) AF: 0.371 AC: 3920 AN: 10558

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19197 AN: 67924

Other (OTH) AF: 0.357 AC: 751 AN: 2106

Alfa AF: 0.322 Hom.: 3707

Bravo AF: 0.358

TwinsUK AF: 0.257 AC: 953

ALSPAC AF: 0.248 AC: 956

ESP6500AA AF: 0.419 AC: 580

ESP6500EA AF: 0.289 AC: 919

ExAC AF: 0.329 AC: 39732

Asia WGS AF: 0.367 AC: 1273 AN: 3476

EpiCase AF: 0.303

EpiControl AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	17
DANN	Benign	0.38
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0098	N
MetaRNN	Benign	0.00044	T;T
MetaSVM	Benign	-0.87	T
PhyloP100		-0.14
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.076
Sift	Benign	0.17	.;T
Sift4G	Benign	0.16	T;T
Polyphen		0.96	.;D
Vest4		0.098
MPC		0.45
ClinPred		0.018	T
GERP RS		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 9

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

Other links and lift over

dbSNP: rs1051792; hg19: chr6-31378977; COSMIC: COSV69826457;