Genetic Variant MICA:c.613+32C>T (chr6-31411391-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001177519.3(MICA):c.613+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,527,512 control chromosomes in the GnomAD database, including 1,891 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 0.040 ( 250 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1641 hom. )

Consequence

MICA
NM_001177519.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Publications

10 publications found

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:

ENSG00000288587 (HGNC:):

ENSG00000288587 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177519.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MICA	NM_001177519.3	MANE Select	c.613+32C>T	intron	N/A	NP_001170990.1	Q96QC4
MICA	NM_001289152.2		c.322+32C>T	intron	N/A	NP_001276081.1	A0A024RCL3
MICA	NM_001289153.2		c.322+32C>T	intron	N/A	NP_001276082.1	A0A024RCL3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MICA	ENST00000449934.7	TSL:1 MANE Select	c.613+32C>T	intron	N/A	ENSP00000413079.1	Q96QC4
MICA	ENST00000892120.1		c.358+32C>T	intron	N/A	ENSP00000562179.1
MICA	ENST00000616296.4	TSL:5	c.322+32C>T	intron	N/A	ENSP00000482382.1	A0A024RCL3

Frequencies

GnomAD3 genomes

AF:

0.0396

AC:

6005

AN:

151794

Hom.:

247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0692

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.0569

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0615

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0366

Gnomad OTH

AF:

0.0422

GnomAD2 exomes

AF:

0.0585

AC:

8107

AN:

138504

AF XY:

0.0544

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.0611

Gnomad FIN exome

AF:

0.0596

Gnomad NFE exome

AF:

0.0396

Gnomad OTH exome

AF:

0.0505

GnomAD4 exome

AF:

0.0357

AC:

49175

AN:

1375600

Hom.:

1641

Cov.:

AF XY:

0.0357

AC XY:

24177

AN XY:

676446

show subpopulations

African (AFR)

AF:

0.0144

AC:

447

AN:

30954

American (AMR)

AF:

0.109

AC:

3645

AN:

33330

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

3944

AN:

23170

East Asian (EAS)

AF:

0.0525

AC:

1869

AN:

35568

South Asian (SAS)

AF:

0.0216

AC:

1634

AN:

75584

European-Finnish (FIN)

AF:

0.0515

AC:

2448

AN:

47572

Middle Eastern (MID)

AF:

0.0455

AC:

254

AN:

5582

European-Non Finnish (NFE)

AF:

0.0303

AC:

32274

AN:

1066826

Other (OTH)

AF:

0.0467

AC:

2660

AN:

57014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2188

4375

6563

8750

10938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1204

2408

3612

4816

6020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0395

AC:

6008

AN:

151912

Hom.:

250

Cov.:

AF XY:

0.0409

AC XY:

3036

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0125

AC:

518

AN:

41342

American (AMR)

AF:

0.0695

AC:

1058

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

679

AN:

3470

East Asian (EAS)

AF:

0.0567

AC:

292

AN:

5152

South Asian (SAS)

AF:

0.0260

AC:

125

AN:

4814

European-Finnish (FIN)

AF:

0.0615

AC:

653

AN:

10610

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0366

AC:

2487

AN:

67996

Other (OTH)

AF:

0.0422

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

286

572

859

1145

1431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0402

Hom.:

612

Bravo

AF:

0.0398

Asia WGS

AF:

0.0360

AC:

126

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.0

(source)

DANN

Benign

0.76

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over