rs41546114

Variant names:

• chr6-31415054-C-T
• rs41546114
• NM_001177519.3:c.*72C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001177519.3(MICA):​c.*72C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00868 in 1,421,268 control chromosomes in the GnomAD database, including 186 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 0.0080 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (163 hom.)
• Consequence: MICA NM_001177519.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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=-0.92).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00799 (1214/151922) while in subpopulation EAS AF = 0.0348 (179/5138). AF 95% confidence interval is 0.0307. There are 23 homozygotes in GnomAd4. There are 648 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.*72C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.*72C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001276081.1
MICA	NM_001289153.2	c.*72C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001276082.1
MICA	NM_001289154.2	c.*72C>T		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.*72C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes AF: 0.00798 AC: 1212 AN: 151804 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00170

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00816

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.0123

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00892

Gnomad OTH AF: 0.00959

GnomAD2 exomes AF: 0.0108 AC: 2700 AN: 248872 AF XY: 0.0117

Gnomad AFR exome AF: 0.00149

Gnomad AMR exome AF: 0.00457

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.0361

Gnomad FIN exome AF: 0.0120

Gnomad NFE exome AF: 0.00912

Gnomad OTH exome AF: 0.00975

GnomAD4 exome AF: 0.00876 AC: 11120 AN: 1269346 Hom.: 163 Cov.: 21 AF XY: 0.00905 AC XY: 5788 AN XY: 639382

Gnomad4 AFR exome AF: 0.00120 AC: 35 AN: 29058

Gnomad4 AMR exome AF: 0.00458 AC: 197 AN: 43020

Gnomad4 ASJ exome AF: 0.00164 AC: 39 AN: 23752

Gnomad4 EAS exome AF: 0.0481 AC: 1750 AN: 36378

Gnomad4 SAS exome AF: 0.0152 AC: 1253 AN: 82192

Gnomad4 FIN exome AF: 0.0118 AC: 588 AN: 49684

Gnomad4 NFE exome AF: 0.00723 AC: 6850 AN: 947612

Gnomad4 Remaining exome AF: 0.00689 AC: 361 AN: 52426

GnomAD4 genome AF: 0.00799 AC: 1214 AN: 151922 Hom.: 23 Cov.: 32 AF XY: 0.00872 AC XY: 648 AN XY: 74286

Gnomad4 AFR AF: 0.00169 AC: 0.00169278 AN: 0.00169278

Gnomad4 AMR AF: 0.00815 AC: 0.00814717 AN: 0.00814717

Gnomad4 ASJ AF: 0.00202 AC: 0.00201845 AN: 0.00201845

Gnomad4 EAS AF: 0.0348 AC: 0.0348385 AN: 0.0348385

Gnomad4 SAS AF: 0.0129 AC: 0.0128845 AN: 0.0128845

Gnomad4 FIN AF: 0.0133 AC: 0.0132893 AN: 0.0132893

Gnomad4 NFE AF: 0.00891 AC: 0.00891072 AN: 0.00891072

Gnomad4 OTH AF: 0.00949 AC: 0.00948767 AN: 0.00948767

Alfa AF: 0.00886 Hom.: 42

Bravo AF: 0.00719

Asia WGS AF: 0.0150 AC: 51 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.8
DANN	Benign	0.66
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

Publications

LitVar

Other links and lift over

dbSNP: rs41546114; hg19: chr6-31382831;