rs2523454

Variant names:

• chr6-31400088-G-A
• rs2523454
• ENST00000745010.1:n.706C>T

Variant summary

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

The ENST00000745010.1(MICA-AS1):​n.706C>T 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 0.315 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-AS1 ENST00000745010.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 44 publications found

Genes affected

MICA-AS1 (HGNC:):

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

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000745010.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA-AS1	NR_148222.1		n.383C>T		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA-AS1	ENST00000745010.1		n.706C>T		non_coding_transcript_exon	Exon 1 of 2
	MICA-AS1	ENST00000745012.1		n.698C>T		non_coding_transcript_exon	Exon 1 of 3
	MICA-AS1	ENST00000745013.1		n.562C>T		non_coding_transcript_exon	Exon 1 of 3

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

African (AFR) AF: 0.104 AC: 1642 AN: 15782

American (AMR) AF: 0.146 AC: 143 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 481 AN: 5148

East Asian (EAS) AF: 0.320 AC: 1160 AN: 3626

South Asian (SAS) AF: 0.162 AC: 2666 AN: 16496

European-Finnish (FIN) AF: 0.311 AC: 87 AN: 280

Middle Eastern (MID) AF: 0.101 AC: 199 AN: 1966

European-Non Finnish (NFE) AF: 0.343 AC: 261690 AN: 761974

Other (OTH) AF: 0.293 AC: 8019 AN: 27322

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

African (AFR) AF: 0.117 AC: 4844 AN: 41376

American (AMR) AF: 0.170 AC: 2590 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 327 AN: 3466

East Asian (EAS) AF: 0.308 AC: 1589 AN: 5158

South Asian (SAS) AF: 0.194 AC: 935 AN: 4824

European-Finnish (FIN) AF: 0.277 AC: 2931 AN: 10582

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20218 AN: 67988

Other (OTH) AF: 0.182 AC: 383 AN: 2108

Alfa AF: 0.276 Hom.: 19975

Bravo AF: 0.212

Asia WGS AF: 0.205 AC: 715 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.79
PhyloP100		-1.9
PromoterAI		-0.011	Neutral

Splicing

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

Other links and lift over

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