6-31412380-TGCTG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001177519.3(MICA):c.953_956del(p.Gly318AlafsTer67) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,527,462 control chromosomes in the GnomAD database, including 9,654 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.15 ( 946 hom., cov: 20)

Exomes 𝑓: 0.11 ( 8708 hom. )

Consequence

MICA
NM_001177519.3 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.131

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-31412380-TGCTG-T is Benign according to our data. Variant chr6-31412380-TGCTG-T is described in ClinVar as [Benign]. Clinvar id is 403086.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MICA	NM_001177519.3 linkuse as main transcript	c.953_956del	p.Gly318AlafsTer67	frameshift_variant	5/6	ENST00000449934.7
MICA	NM_001289152.2 linkuse as main transcript	c.662_665del	p.Gly221AlafsTer67	frameshift_variant	5/6
MICA	NM_001289153.2 linkuse as main transcript	c.662_665del	p.Gly221AlafsTer67	frameshift_variant	5/6
MICA	NM_001289154.2 linkuse as main transcript	c.539_542del	p.Gly180AlafsTer67	frameshift_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MICA	ENST00000449934.7 linkuse as main transcript	c.953_956del	p.Gly318AlafsTer67	frameshift_variant	5/6	1	NM_001177519.3	P1
MICA	ENST00000421350.1 linkuse as main transcript	c.626_629del	p.Gly209AlafsTer67	frameshift_variant	4/5	5
MICA	ENST00000616296.4 linkuse as main transcript	c.662_665del	p.Gly221AlafsTer67	frameshift_variant	5/6	5
MICA	ENST00000674069.1 linkuse as main transcript	c.539_542del	p.Gly180AlafsTer67	frameshift_variant	5/6

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

15660

AN:

102830

Hom.:

939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.158

AC:

17598

AN:

111472

Hom.:

1176

AF XY:

0.156

AC XY:

9334

AN XY:

59832

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.106

AC:

151295

AN:

1424570

Hom.:

8708

AF XY:

0.106

AC XY:

74757

AN XY:

705794

show subpopulations

Gnomad4 AFR exome

AF:

0.0763

Gnomad4 AMR exome

AF:

0.0717

Gnomad4 ASJ exome

AF:

0.0818

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.0717

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.152

AC:

15683

AN:

102892

Hom.:

946

Cov.:

AF XY:

0.157

AC XY:

7771

AN XY:

49540

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.166

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.177

Alfa

AF:

0.103

Hom.:

Bravo

AF:

0.0981

Asia WGS

AF:

0.263

AC:

571

AN:

2178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 2994/11918=25.12% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over