6-31415134-A-G

Variant names:

• chr6-31415134-A-G
• rs1882
• NM_001177519.3:c.*152A>G

Variant summary

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

The NM_001177519.3(MICA):​c.*152A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,020,480 control chromosomes in the GnomAD database, including 152,805 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 0.61 (28902 hom., cov: 30)
  • Exomes 𝑓: 0.50 (123903 hom.)
• Consequence: MICA NM_001177519.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 33 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177519.3. 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	NM_001177519.3	MANE Select	c.*152A>G		3_prime_UTR	Exon 6 of 6	NP_001170990.1
	MICA	NM_001289152.2		c.*152A>G		3_prime_UTR	Exon 6 of 6	NP_001276081.1
	MICA	NM_001289153.2		c.*152A>G		3_prime_UTR	Exon 6 of 6	NP_001276082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	ENST00000449934.7	TSL:1 MANE Select	c.*152A>G		3_prime_UTR	Exon 6 of 6	ENSP00000413079.1
	MICA	ENST00000616296.4	TSL:5	c.*152A>G		3_prime_UTR	Exon 6 of 6	ENSP00000482382.1
	MICA	ENST00000421350.1	TSL:5	c.*152A>G		3_prime_UTR	Exon 5 of 5	ENSP00000402410.1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 91743 AN: 151104 Hom.: 28854 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.688

GnomAD2 exomes AF: 0.634 AC: 156211 AN: 246494 AF XY: 0.632

Gnomad AFR exome AF: 0.669

Gnomad AMR exome AF: 0.821

Gnomad ASJ exome AF: 0.804

Gnomad EAS exome AF: 0.763

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.522

Gnomad OTH exome AF: 0.650

GnomAD4 exome AF: 0.501 AC: 435397 AN: 869256 Hom.: 123903 Cov.: 13 AF XY: 0.515 AC XY: 234043 AN XY: 454546

African (AFR) AF: 0.633 AC: 12424 AN: 19614

American (AMR) AF: 0.815 AC: 34026 AN: 41760

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 15896 AN: 20284

East Asian (EAS) AF: 0.814 AC: 27670 AN: 34000

South Asian (SAS) AF: 0.733 AC: 53240 AN: 72638

European-Finnish (FIN) AF: 0.553 AC: 27009 AN: 48848

Middle Eastern (MID) AF: 0.733 AC: 3106 AN: 4238

European-Non Finnish (NFE) AF: 0.409 AC: 241271 AN: 589392

Other (OTH) AF: 0.539 AC: 20755 AN: 38482

GnomAD4 genome AF: 0.607 AC: 91847 AN: 151224 Hom.: 28902 Cov.: 30 AF XY: 0.617 AC XY: 45637 AN XY: 73914

African (AFR) AF: 0.662 AC: 27190 AN: 41052

American (AMR) AF: 0.748 AC: 11336 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2756 AN: 3454

East Asian (EAS) AF: 0.779 AC: 3964 AN: 5090

South Asian (SAS) AF: 0.778 AC: 3732 AN: 4796

European-Finnish (FIN) AF: 0.565 AC: 5938 AN: 10508

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34773 AN: 67874

Other (OTH) AF: 0.692 AC: 1455 AN: 2102

Alfa AF: 0.566 Hom.: 16076

Bravo AF: 0.625

Asia WGS AF: 0.768 AC: 2668 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.9
DANN	Benign	0.45
PhyloP100		-0.29
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: rs1882; hg19: chr6-31382911; COSMIC: COSV108251204;