rs2523454

Variant names:

• chr6-31400088-G-A
• rs2523454
• ENST00000616296:c.-917G>A

Variant summary

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

The ENST00000616296(MICA):​c.-917G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 985,492 control chromosomes in the GnomAD database, including 51,879 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 0.22 (4628 hom., cov: 33)
  • Exomes 𝑓: 0.33 (47251 hom.)
• Consequence: MICA ENST00000616296 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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-AS1 (HGNC:53631): (MICA antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA-AS1	NR_148222.1	n.383C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000616296	c.-917G>A		5_prime_UTR_variant	Exon 1 of 6	5		ENSP00000482382.1
MICA	ENST00000674069	c.-848G>A		5_prime_UTR_variant	Exon 1 of 6			ENSP00000501157.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34128 AN: 151800 Hom.: 4629 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.331 AC: 276087 AN: 833576 Hom.: 47251 Cov.: 35 AF XY: 0.333 AC XY: 128028 AN XY: 384986

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.0934

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.225 AC: 34128 AN: 151916 Hom.: 4628 Cov.: 33 AF XY: 0.221 AC XY: 16430 AN XY: 74270

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0943

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.182

Alfa AF: 0.273 Hom.: 6244

Bravo AF: 0.212

Asia WGS AF: 0.205 AC: 715 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523454; hg19: chr6-31367865; COSMIC: COSV63026500; COSMIC: COSV63026500;