Variant chr6-31411996-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001177519.3(MICA):c.663C>T(p.Ile221=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,607,520 control chromosomes in the GnomAD database, including 73,740 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 0.35 ( 10060 hom., cov: 31)

Exomes 𝑓: 0.29 ( 63680 hom. )

Consequence

MICA
NM_001177519.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.161

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 (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MICA	NM_001177519.3 linkuse as main transcript	c.663C>T	p.Ile221=	synonymous_variant	4/6	ENST00000449934.7
MICA	NM_001289152.2 linkuse as main transcript	c.372C>T	p.Ile124=	synonymous_variant	4/6
MICA	NM_001289153.2 linkuse as main transcript	c.372C>T	p.Ile124=	synonymous_variant	4/6
MICA	NM_001289154.2 linkuse as main transcript	c.249C>T	p.Ile83=	synonymous_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MICA	ENST00000449934.7 linkuse as main transcript	c.663C>T	p.Ile221=	synonymous_variant	4/6	1	NM_001177519.3	P1
MICA	ENST00000616296.4 linkuse as main transcript	c.372C>T	p.Ile124=	synonymous_variant	4/6	5
MICA	ENST00000421350.1 linkuse as main transcript	c.336C>T	p.Ile112=	synonymous_variant	3/5	5
MICA	ENST00000674069.1 linkuse as main transcript	c.249C>T	p.Ile83=	synonymous_variant	4/6

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53333

AN:

151508

Hom.:

10041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.354

GnomAD3 exomes

AF:

0.322

AC:

76546

AN:

237744

Hom.:

13951

AF XY:

0.314

AC XY:

40402

AN XY:

128800

show subpopulations

Gnomad AFR exome

AF:

0.446

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.447

Gnomad EAS exome

AF:

0.332

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.286

AC:

416372

AN:

1455894

Hom.:

63680

Cov.:

AF XY:

0.286

AC XY:

207278

AN XY:

723964

show subpopulations

Gnomad4 AFR exome

AF:

0.456

Gnomad4 AMR exome

AF:

0.448

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.300

Gnomad4 FIN exome

AF:

0.348

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.352

AC:

53398

AN:

151626

Hom.:

10060

Cov.:

AF XY:

0.356

AC XY:

26388

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.445

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.337

Hom.:

2017

Bravo

AF:

0.358

Asia WGS

AF:

0.365

AC:

1269

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.3

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)

0.020

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