rs1051796

Variant names:

• chr6-31411996-C-T
• rs1051796
• NM_001177519.3:c.663C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001177519.3(MICA):​c.663C>T​(p.Ile221Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,607,520 control chromosomes in the GnomAD database, including 73,740 homozygotes. In-silico tool predicts 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 (10060 hom., cov: 31)
  • Exomes 𝑓: 0.29 (63680 hom.)
• Consequence: MICA NM_001177519.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.663C>T	p.Ile221Ile	synonymous_variant	Exon 4 of 6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.372C>T	p.Ile124Ile	synonymous_variant	Exon 4 of 6		NP_001276081.1
MICA	NM_001289153.2	c.372C>T	p.Ile124Ile	synonymous_variant	Exon 4 of 6		NP_001276082.1
MICA	NM_001289154.2	c.249C>T	p.Ile83Ile	synonymous_variant	Exon 4 of 6		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.663C>T	p.Ile221Ile	synonymous_variant	Exon 4 of 6	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53333 AN: 151508 Hom.: 10041 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.354

GnomAD2 exomes AF: 0.322 AC: 76546 AN: 237744 AF XY: 0.314

Gnomad AFR exome AF: 0.446

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.332

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.310

GnomAD4 exome AF: 0.286 AC: 416372 AN: 1455894 Hom.: 63680 Cov.: 54 AF XY: 0.286 AC XY: 207278 AN XY: 723964

African (AFR) AF: 0.456 AC: 15189 AN: 33318

American (AMR) AF: 0.448 AC: 19676 AN: 43946

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 11712 AN: 25732

East Asian (EAS) AF: 0.305 AC: 12080 AN: 39624

South Asian (SAS) AF: 0.300 AC: 25681 AN: 85608

European-Finnish (FIN) AF: 0.348 AC: 18488 AN: 53062

Middle Eastern (MID) AF: 0.296 AC: 1681 AN: 5688

European-Non Finnish (NFE) AF: 0.264 AC: 293181 AN: 1108782

Other (OTH) AF: 0.311 AC: 18684 AN: 60134

GnomAD4 genome AF: 0.352 AC: 53398 AN: 151626 Hom.: 10060 Cov.: 31 AF XY: 0.356 AC XY: 26388 AN XY: 74116

African (AFR) AF: 0.445 AC: 18362 AN: 41224

American (AMR) AF: 0.392 AC: 5963 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1611 AN: 3458

East Asian (EAS) AF: 0.317 AC: 1627 AN: 5138

South Asian (SAS) AF: 0.306 AC: 1473 AN: 4814

European-Finnish (FIN) AF: 0.371 AC: 3920 AN: 10562

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19180 AN: 67914

Other (OTH) AF: 0.357 AC: 752 AN: 2106

Alfa AF: 0.340 Hom.: 2111

Bravo AF: 0.358

Asia WGS AF: 0.365 AC: 1269 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs1051796; hg19: chr6-31379773; COSMIC: COSV69826885;