rs1882

Positions:

• chr6-31415134-A-G
• chr6-31415134-A-T

Variant summary

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

The ENST00000449934.7(MICA):​c.*152A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,020,480 control chromosomes in the GnomAD database, including 152,805 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 0.61 (28902 hom., cov: 30)
  • Exomes 𝑓: 0.50 (123903 hom.)
• Consequence: MICA ENST00000449934.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICA	NM_001177519.3	c.*152A>G		3_prime_UTR_variant	6/6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.*152A>G		3_prime_UTR_variant	6/6		NP_001276081.1
MICA	NM_001289153.2	c.*152A>G		3_prime_UTR_variant	6/6		NP_001276082.1
MICA	NM_001289154.2	c.*152A>G		3_prime_UTR_variant	6/6		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.*152A>G		3_prime_UTR_variant	6/6	1	NM_001177519.3	ENSP00000413079	P1
MICA	ENST00000421350.1	c.*152A>G		3_prime_UTR_variant	5/5	5		ENSP00000402410
MICA	ENST00000616296.4	c.*152A>G		3_prime_UTR_variant	6/6	5		ENSP00000482382
MICA	ENST00000674069.1	c.*152A>G		3_prime_UTR_variant	6/6			ENSP00000501157

Frequencies

GnomAD3 genomes AF: 0.607 AC: 91743 AN: 151104 Hom.: 28854 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.688

GnomAD3 exomes AF: 0.634 AC: 156211 AN: 246494 Hom.: 52239 AF XY: 0.632 AC XY: 84584 AN XY: 133860

Gnomad AFR exome AF: 0.669

Gnomad AMR exome AF: 0.821

Gnomad ASJ exome AF: 0.804

Gnomad EAS exome AF: 0.763

Gnomad SAS exome AF: 0.736

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.522

Gnomad OTH exome AF: 0.650

GnomAD4 exome AF: 0.501 AC: 435397 AN: 869256 Hom.: 123903 Cov.: 13 AF XY: 0.515 AC XY: 234043 AN XY: 454546

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.784

Gnomad4 EAS exome AF: 0.814

Gnomad4 SAS exome AF: 0.733

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.539

GnomAD4 genome AF: 0.607 AC: 91847 AN: 151224 Hom.: 28902 Cov.: 30 AF XY: 0.617 AC XY: 45637 AN XY: 73914

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.692

Alfa AF: 0.556 Hom.: 11471

Bravo AF: 0.625

Asia WGS AF: 0.768 AC: 2668 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.9
DANN	Benign	0.45
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: rs1882; hg19: chr6-31382911;