rs12175489

Positions:

• chr6-31409810-G-A
• chr6-31409810-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.71-733G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,594 control chromosomes in the GnomAD database, including 1,632 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 0.13 (1632 hom., cov: 32)
• Consequence: MICA NM_001177519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICA	NM_001177519.3	c.71-733G>A		intron_variant		ENST00000449934.7
MICA	NM_001289152.2	c.-221-733G>A		intron_variant
MICA	NM_001289153.2	c.-221-733G>A		intron_variant
MICA	NM_001289154.2	c.-172-733G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICA	ENST00000449934.7	c.71-733G>A		intron_variant		1	NM_001177519.3	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19171 AN: 151476 Hom.: 1630 Cov.: 32

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19178 AN: 151594 Hom.: 1632 Cov.: 32 AF XY: 0.130 AC XY: 9637 AN XY: 74062

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.135

Alfa AF: 0.134 Hom.: 944

Bravo AF: 0.124

Asia WGS AF: 0.263 AC: 911 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.24

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: rs12175489; hg19: chr6-31377587;