rs3763288

Variant names:

• chr6-31402590-G-A
• rs3763288
• ENST00000667609.1:n.498G>A

Variant summary

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

The ENST00000667609.1(MICA):​n.498G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 151,936 control chromosomes in the GnomAD database, including 382 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 0.054 (382 hom., cov: 31)
• Consequence: MICA ENST00000667609.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 24 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001289152.2	c.-222+1807G>A		intron_variant	Intron 1 of 5		NP_001276081.1
MICA	NM_001289153.2	c.-222+1827G>A		intron_variant	Intron 1 of 5		NP_001276082.1
MICA	NM_001289154.2	c.-173+1827G>A		intron_variant	Intron 1 of 5		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000667609.1	n.498G>A		non_coding_transcript_exon_variant	Exon 2 of 2
MICA	ENST00000616296.4	c.-222+1807G>A		intron_variant	Intron 1 of 5	5		ENSP00000482382.1
MICA	ENST00000674069.1	c.-173+1827G>A		intron_variant	Intron 1 of 5			ENSP00000501157.1

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8261 AN: 151818 Hom.: 382 Cov.: 31

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0543 AC: 8256 AN: 151936 Hom.: 382 Cov.: 31 AF XY: 0.0572 AC XY: 4249 AN XY: 74292

African (AFR) AF: 0.0129 AC: 534 AN: 41380

American (AMR) AF: 0.0596 AC: 906 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.189 AC: 976 AN: 5164

South Asian (SAS) AF: 0.0338 AC: 163 AN: 4818

European-Finnish (FIN) AF: 0.121 AC: 1283 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0630 AC: 4287 AN: 67996

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0639 Hom.: 1538

Bravo AF: 0.0516

Asia WGS AF: 0.0670 AC: 234 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.57
PhyloP100		-0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3763288; hg19: chr6-31370367;