Genetic Variant NM_001177519.3:c.261G>A (chr6-31410733-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001177519.3(MICA):c.261G>A(p.Arg87Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,604,506 control chromosomes in the GnomAD database, including 3,853 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 0.066 ( 437 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3416 hom. )

Consequence

MICA
NM_001177519.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.149

Publications

23 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.092).

BP7

Synonymous conserved (PhyloP=-0.149 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3 link	c.261G>A	p.Arg87Arg	synonymous_variant	Exon 2 of 6	ENST00000449934.7	NP_001170990.1	Q96QC4
MICA	NM_001289154.2 link	c.19G>A	p.Gly7Arg	missense_variant	Exon 2 of 6		NP_001276083.1	Q96QC4A0A0G2JJ55
MICA	NM_001289152.2 link	c.-31G>A		5_prime_UTR_variant	Exon 2 of 6		NP_001276081.1	Q96QC4A0A024RCL3
MICA	NM_001289153.2 link	c.-31G>A		5_prime_UTR_variant	Exon 2 of 6		NP_001276082.1	Q96QC4A0A024RCL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7 link	c.261G>A	p.Arg87Arg	synonymous_variant	Exon 2 of 6	1	NM_001177519.3	ENSP00000413079.1		Q96QC4

Frequencies

GnomAD3 genomes

AF:

0.0663

AC:

10074

AN:

151852

Hom.:

433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0697

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0607

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.0849

Gnomad SAS

AF:

0.0450

Gnomad FIN

AF:

0.0570

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0679

Gnomad OTH

AF:

0.0747

GnomAD2 exomes

AF:

0.0641

AC:

14801

AN:

230786

AF XY:

0.0643

show subpopulations

Gnomad AFR exome

AF:

0.0684

Gnomad AMR exome

AF:

0.0518

Gnomad ASJ exome

AF:

0.0623

Gnomad EAS exome

AF:

0.0822

Gnomad FIN exome

AF:

0.0563

Gnomad NFE exome

AF:

0.0700

Gnomad OTH exome

AF:

0.0746

GnomAD4 exome

AF:

0.0626

AC:

90894

AN:

1452536

Hom.:

3416

Cov.:

AF XY:

0.0629

AC XY:

45433

AN XY:

721940

show subpopulations

African (AFR)

AF:

0.0641

AC:

2134

AN:

33274

American (AMR)

AF:

0.0520

AC:

2185

AN:

41992

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

1648

AN:

25992

East Asian (EAS)

AF:

0.107

AC:

4192

AN:

39228

South Asian (SAS)

AF:

0.0480

AC:

4092

AN:

85298

European-Finnish (FIN)

AF:

0.0564

AC:

2994

AN:

53050

Middle Eastern (MID)

AF:

0.0944

AC:

544

AN:

5760

European-Non Finnish (NFE)

AF:

0.0625

AC:

69230

AN:

1107816

Other (OTH)

AF:

0.0644

AC:

3875

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

5119

10237

15356

20474

25593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2434

4868

7302

9736

12170

<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:

0.0664

AC:

10092

AN:

151970

Hom.:

437

Cov.:

AF XY:

0.0668

AC XY:

4960

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0696

AC:

2879

AN:

41378

American (AMR)

AF:

0.0607

AC:

924

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.0576

AC:

200

AN:

3470

East Asian (EAS)

AF:

0.0851

AC:

439

AN:

5156

South Asian (SAS)

AF:

0.0453

AC:

218

AN:

4816

European-Finnish (FIN)

AF:

0.0570

AC:

604

AN:

10600

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0679

AC:

4621

AN:

68010

Other (OTH)

AF:

0.0801

AC:

169

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

494

987

1481

1974

2468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0679

Hom.:

1553

Bravo

AF:

0.0658

Asia WGS

AF:

0.104

AC:

363

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.2

(source)

DANN

Benign

0.50

PhyloP100

-0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over