rs12175489

Variant names:

• chr6-31409810-G-A
• rs12175489
• NM_001177519.3:c.71-733G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31409810-G-A
• chr6-31409810-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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=-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 rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.71-733G>A		intron_variant	Intron 1 of 5	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.-221-733G>A		intron_variant	Intron 1 of 5		NP_001276081.1
MICA	NM_001289153.2	c.-221-733G>A		intron_variant	Intron 1 of 5		NP_001276082.1
MICA	NM_001289154.2	c.-172-733G>A		intron_variant	Intron 1 of 5		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.71-733G>A		intron_variant	Intron 1 of 5	1	NM_001177519.3	ENSP00000413079.1

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

African (AFR) AF: 0.0725 AC: 2991 AN: 41230

American (AMR) AF: 0.143 AC: 2162 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 636 AN: 3462

East Asian (EAS) AF: 0.336 AC: 1727 AN: 5134

South Asian (SAS) AF: 0.167 AC: 803 AN: 4802

European-Finnish (FIN) AF: 0.145 AC: 1536 AN: 10560

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8960 AN: 67940

Other (OTH) AF: 0.135 AC: 285 AN: 2106

Alfa AF: 0.123 Hom.: 1264

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
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12175489; hg19: chr6-31377587;