rs9266825

Positions:

• chr6-31415105-C-A
• chr6-31415105-C-T

Variant summary

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

The NM_001177519.3(MICA):​c.*123C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,202,572 control chromosomes in the GnomAD database, including 44,966 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 0.32 (8322 hom., cov: 31)
  • Exomes 𝑓: 0.25 (36644 hom.)
• Consequence: MICA NM_001177519.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICA	NM_001177519.3	c.*123C>A		3_prime_UTR_variant	6/6	ENST00000449934.7
MICA	NM_001289152.2	c.*123C>A		3_prime_UTR_variant	6/6
MICA	NM_001289153.2	c.*123C>A		3_prime_UTR_variant	6/6
MICA	NM_001289154.2	c.*123C>A		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICA	ENST00000449934.7	c.*123C>A		3_prime_UTR_variant	6/6	1	NM_001177519.3	P1
MICA	ENST00000421350.1	c.*123C>A		3_prime_UTR_variant	5/5	5
MICA	ENST00000616296.4	c.*123C>A		3_prime_UTR_variant	6/6	5
MICA	ENST00000674069.1	c.*123C>A		3_prime_UTR_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48388 AN: 151400 Hom.: 8304 Cov.: 31

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.305

GnomAD3 exomes AF: 0.310 AC: 77028 AN: 248426 Hom.: 13293 AF XY: 0.305 AC XY: 41161 AN XY: 134872

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.406

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.338

Gnomad SAS exome AF: 0.290

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.247 AC: 259741 AN: 1051054 Hom.: 36644 Cov.: 17 AF XY: 0.251 AC XY: 135269 AN XY: 539760

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.320 AC: 48456 AN: 151518 Hom.: 8322 Cov.: 31 AF XY: 0.326 AC XY: 24170 AN XY: 74030

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.309

Alfa AF: 0.263 Hom.: 5132

Bravo AF: 0.321

Asia WGS AF: 0.361 AC: 1253 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs9266825; hg19: chr6-31382882; COSMIC: COSV69827138;