Variant 6-31411179-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000449934.7(MICA):c.433C>G(p.Leu145Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,612,840 control chromosomes in the GnomAD database, including 25,341 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3169 hom., cov: 31)

Exomes 𝑓: 0.16 ( 22172 hom. )

Consequence

MICA
ENST00000449934.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.826

Variant links:

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]

MICA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060625076).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MICA	NM_001177519.3 linkuse as main transcript	c.433C>G	p.Leu145Val	missense_variant	3/6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2 linkuse as main transcript	c.142C>G	p.Leu48Val	missense_variant	3/6		NP_001276081.1
MICA	NM_001289153.2 linkuse as main transcript	c.142C>G	p.Leu48Val	missense_variant	3/6		NP_001276082.1
MICA	NM_001289154.2 linkuse as main transcript	c.84-65C>G		intron_variant			NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7 linkuse as main transcript	c.433C>G	p.Leu145Val	missense_variant	3/6	1	NM_001177519.3	ENSP00000413079	P1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28119

AN:

151688

Hom.:

3161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.0779

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.262

GnomAD3 exomes

AF:

0.171

AC:

42488

AN:

248204

Hom.:

4710

AF XY:

0.179

AC XY:

24108

AN XY:

134734

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.0959

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.0785

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.161

AC:

235891

AN:

1461034

Hom.:

22172

Cov.:

AF XY:

0.166

AC XY:

120488

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.0805

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.185

AC:

28146

AN:

151806

Hom.:

3169

Cov.:

AF XY:

0.185

AC XY:

13702

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.277

Gnomad4 FIN

AF:

0.0779

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.138

Hom.:

572

Bravo

AF:

0.200

TwinsUK

AF:

0.136

AC:

504

ALSPAC

AF:

0.150

AC:

580

ESP6500AA

AF:

0.244

AC:

338

ESP6500EA

AF:

0.154

AC:

489

ExAC

AF:

0.174

AC:

21072

Asia WGS

AF:

0.185

AC:

644

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.5

DANN

Benign

0.96

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.043

MetaRNN

Benign

0.0061

T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.85

.;N

REVEL

Benign

0.047

Sift

Benign

0.085

.;T

Sift4G

Benign

0.23

T;T

Polyphen

1.0

.;D

Vest4

0.078

MPC

0.53

ClinPred

0.010

GERP RS

1.9

gMVP

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over