rs2523451

Positions:

• chr6-31401374-G-A

Variant summary

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

The NM_001289152.2(MICA):​c.-222+591G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,658 control chromosomes in the GnomAD database, including 5,644 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 0.26 (5644 hom., cov: 32)
• Consequence: MICA NM_001289152.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.947

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]

MICA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICA	NM_001289152.2	c.-222+591G>A		intron_variant			NP_001276081.1
MICA	NM_001289153.2	c.-222+611G>A		intron_variant			NP_001276082.1
MICA	NM_001289154.2	c.-173+611G>A		intron_variant			NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000616296.4	c.-222+591G>A		intron_variant		5		ENSP00000482382.1
MICA	ENST00000674069.1	c.-173+611G>A		intron_variant				ENSP00000501157.1
MICA	ENST00000673647.1	c.-389+611G>A		intron_variant				ENSP00000500967.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39816 AN: 151540 Hom.: 5645 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.263 AC: 39827 AN: 151658 Hom.: 5644 Cov.: 32 AF XY: 0.259 AC XY: 19170 AN XY: 74136

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.222

Alfa AF: 0.278 Hom.: 1203

Bravo AF: 0.256

Asia WGS AF: 0.222 AC: 771 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523451; hg19: chr6-31369151;