rs1063632

chr6-31410733-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001177519.3(MICA):c.261G>A(p.Arg87=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,604,506 control chromosomes in the GnomAD database, including 3,853 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 0.066 (437 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3416 hom.)
• Consequence: MICA NM_001177519.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-0.149 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICA	NM_001177519.3	c.261G>A	p.Arg87=	synonymous_variant	2/6	ENST00000449934.7
MICA	NM_001289154.2	c.19G>A	p.Gly7Arg	missense_variant	2/6
MICA	NM_001289152.2	c.-31G>A		5_prime_UTR_variant	2/6
MICA	NM_001289153.2	c.-31G>A		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICA	ENST00000449934.7	c.261G>A	p.Arg87=	synonymous_variant	2/6	1	NM_001177519.3	P1

Frequencies

GnomAD3 genomes AF: 0.0663 AC: 10074 AN: 151852 Hom.: 433 Cov.: 32

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0570

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.0747

GnomAD3 exomes AF: 0.0641 AC: 14801 AN: 230786 Hom.: 615 AF XY: 0.0643 AC XY: 8057 AN XY: 125376

Gnomad AFR exome AF: 0.0684

Gnomad AMR exome AF: 0.0518

Gnomad ASJ exome AF: 0.0623

Gnomad EAS exome AF: 0.0822

Gnomad SAS exome AF: 0.0485

Gnomad FIN exome AF: 0.0563

Gnomad NFE exome AF: 0.0700

Gnomad OTH exome AF: 0.0746

GnomAD4 exome AF: 0.0626 AC: 90894 AN: 1452536 Hom.: 3416 Cov.: 37 AF XY: 0.0629 AC XY: 45433 AN XY: 721940

Gnomad4 AFR exome AF: 0.0641

Gnomad4 AMR exome AF: 0.0520

Gnomad4 ASJ exome AF: 0.0634

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.0480

Gnomad4 FIN exome AF: 0.0564

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.0644

GnomAD4 genome AF: 0.0664 AC: 10092 AN: 151970 Hom.: 437 Cov.: 32 AF XY: 0.0668 AC XY: 4960 AN XY: 74306

Gnomad4 AFR AF: 0.0696

Gnomad4 AMR AF: 0.0607

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.0851

Gnomad4 SAS AF: 0.0453

Gnomad4 FIN AF: 0.0570

Gnomad4 NFE AF: 0.0679

Gnomad4 OTH AF: 0.0801

Alfa AF: 0.0705 Hom.: 697

Bravo AF: 0.0658

Asia WGS AF: 0.104 AC: 363 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	1.2
Dann	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1063632; hg19: chr6-31378510; COSMIC: COSV69826567;