Genetic Variant NM_001177519.3:c.*30-656T>C (chr6-31414356-T-C) – 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.*30-656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,424 control chromosomes in the GnomAD database, including 8,309 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 0.32 ( 8309 hom., cov: 33)

Consequence

MICA
NM_001177519.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.561

Publications

4 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:

Genome browser will be placed here

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=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 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.*30-656T>C	intron	N/A	NP_001170990.1	Q96QC4
MICA	NM_001289152.2		c.*30-656T>C	intron	N/A	NP_001276081.1	A0A024RCL3
MICA	NM_001289153.2		c.*30-656T>C	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.*30-656T>C	intron	N/A	ENSP00000413079.1	Q96QC4
MICA	ENST00000892120.1		c.*30-656T>C	intron	N/A	ENSP00000562179.1
MICA	ENST00000616296.4	TSL:5	c.*30-656T>C	intron	N/A	ENSP00000482382.1	A0A024RCL3

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48441

AN:

151306

Hom.:

8291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.320

AC:

48509

AN:

151424

Hom.:

8309

Cov.:

AF XY:

0.327

AC XY:

24176

AN XY:

73966

show subpopulations

African (AFR)

AF:

0.398

AC:

16414

AN:

41190

American (AMR)

AF:

0.349

AC:

5303

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1216

AN:

3468

East Asian (EAS)

AF:

0.317

AC:

1627

AN:

5132

South Asian (SAS)

AF:

0.304

AC:

1457

AN:

4790

European-Finnish (FIN)

AF:

0.369

AC:

3871

AN:

10498

Middle Eastern (MID)

AF:

0.346

AC:

101

AN:

292

European-Non Finnish (NFE)

AF:

0.257

AC:

17469

AN:

67858

Other (OTH)

AF:

0.311

AC:

652

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1689

3378

5067

6756

8445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.283

Hom.:

794

Bravo

AF:

0.321

Asia WGS

AF:

0.361

AC:

1254

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.0

(source)

DANN

Benign

0.59

PhyloP100

-0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over