rs41546114

chr6-31415054-C-T

Variant summary

Our verdict is Benign. Variant got -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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICA	NM_001177519.3	c.*72C>T		3_prime_UTR_variant	6/6	ENST00000449934.7
MICA	NM_001289152.2	c.*72C>T		3_prime_UTR_variant	6/6
MICA	NM_001289153.2	c.*72C>T		3_prime_UTR_variant	6/6
MICA	NM_001289154.2	c.*72C>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICA	ENST00000449934.7	c.*72C>T		3_prime_UTR_variant	6/6	1	NM_001177519.3	P1
MICA	ENST00000421350.1	c.*72C>T		3_prime_UTR_variant	5/5	5
MICA	ENST00000616296.4	c.*72C>T		3_prime_UTR_variant	6/6	5
MICA	ENST00000674069.1	c.*72C>T		3_prime_UTR_variant	6/6

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

GnomAD3 exomes AF: 0.0108 AC: 2700 AN: 248872 Hom.: 55 AF XY: 0.0117 AC XY: 1579 AN XY: 135098

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 SAS exome AF: 0.0165

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

Gnomad4 AMR exome AF: 0.00458

Gnomad4 ASJ exome AF: 0.00164

Gnomad4 EAS exome AF: 0.0481

Gnomad4 SAS exome AF: 0.0152

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.00723

Gnomad4 OTH exome AF: 0.00689

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

Gnomad4 AMR AF: 0.00815

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0348

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.00891

Gnomad4 OTH AF: 0.00949

Alfa AF: 0.00710 Hom.: 3

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

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;