chr6-31415105-C-A

Variant names:

• chr6-31415105-C-A
• rs9266825
• NM_001177519.3:c.*123C>A

Variant summary

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

The NM_001177519.3(MICA):​c.*123C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,202,572 control chromosomes in the GnomAD database, including 44,966 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 0.32 (8322 hom., cov: 31)
  • Exomes 𝑓: 0.25 (36644 hom.)
• Consequence: MICA NM_001177519.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 43 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.*123C>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.*123C>A		3_prime_UTR_variant	Exon 6 of 6		NP_001276081.1
MICA	NM_001289153.2	c.*123C>A		3_prime_UTR_variant	Exon 6 of 6		NP_001276082.1
MICA	NM_001289154.2	c.*123C>A		3_prime_UTR_variant	Exon 6 of 6		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.*123C>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48388 AN: 151400 Hom.: 8304 Cov.: 31

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.310 AC: 77028 AN: 248426 AF XY: 0.305

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.406

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.338

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.247 AC: 259741 AN: 1051054 Hom.: 36644 Cov.: 17 AF XY: 0.251 AC XY: 135269 AN XY: 539760

African (AFR) AF: 0.387 AC: 9057 AN: 23418

American (AMR) AF: 0.399 AC: 16824 AN: 42200

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 7100 AN: 21620

East Asian (EAS) AF: 0.276 AC: 9443 AN: 34268

South Asian (SAS) AF: 0.296 AC: 22659 AN: 76536

European-Finnish (FIN) AF: 0.335 AC: 16419 AN: 49074

Middle Eastern (MID) AF: 0.250 AC: 1154 AN: 4614

European-Non Finnish (NFE) AF: 0.219 AC: 165587 AN: 754614

Other (OTH) AF: 0.257 AC: 11498 AN: 44710

GnomAD4 genome AF: 0.320 AC: 48456 AN: 151518 Hom.: 8322 Cov.: 31 AF XY: 0.326 AC XY: 24170 AN XY: 74030

African (AFR) AF: 0.398 AC: 16374 AN: 41168

American (AMR) AF: 0.349 AC: 5292 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1216 AN: 3466

East Asian (EAS) AF: 0.315 AC: 1613 AN: 5120

South Asian (SAS) AF: 0.303 AC: 1452 AN: 4798

European-Finnish (FIN) AF: 0.369 AC: 3895 AN: 10554

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17463 AN: 67932

Other (OTH) AF: 0.309 AC: 649 AN: 2100

Alfa AF: 0.263 Hom.: 8780

Bravo AF: 0.321

Asia WGS AF: 0.361 AC: 1253 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.84
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9266825; hg19: chr6-31382882; COSMIC: COSV69827138;