Genetic Variant MICA-AS1:n.343G>A (chr6-31395153-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 ENST00000606743.1(MICA-AS1):n.343G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 955,144 control chromosomes in the GnomAD database, including 56,944 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 0.40 ( 12824 hom., cov: 26)

Exomes 𝑓: 0.32 ( 44120 hom. )

Consequence

MICA-AS1
ENST00000606743.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

43 publications found

Variant links:

COSMIC-nc: COSV74094080

Genes affected

MICA-AS1 (HGNC:):

MICA-AS1 links:

MICA-AS1 (HGNC:53631): (MICA antisense RNA 1)

MICA-AS1 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=-1.06).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA-AS1	NR_148222.1 link	n.482G>A		non_coding_transcript_exon_variant	Exon 2 of 2
MICA-AS1	NR_148223.1 link	n.515G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MICA-AS1	ENST00000606743.1 link	n.343G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
MICA-AS1	ENST00000745010.1 link	n.805G>A	non_coding_transcript_exon_variant	Exon 2 of 2
MICA-AS1	ENST00000745011.1 link	n.742G>A	non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

58535

AN:

145622

Hom.:

12801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.515

Gnomad AMI

AF:

0.494

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.477

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.456

GnomAD4 exome

AF:

0.315

AC:

255015

AN:

809406

Hom.:

44120

Cov.:

AF XY:

0.314

AC XY:

117319

AN XY:

373888

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.558

AC:

8601

AN:

15416

American (AMR)

AF:

0.551

AC:

529

AN:

960

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

3155

AN:

5018

East Asian (EAS)

AF:

0.363

AC:

1291

AN:

3556

South Asian (SAS)

AF:

0.399

AC:

6415

AN:

16060

European-Finnish (FIN)

AF:

0.310

AC:

AN:

268

Middle Eastern (MID)

AF:

0.475

AC:

754

AN:

1586

European-Non Finnish (NFE)

AF:

0.303

AC:

224558

AN:

740010

Other (OTH)

AF:

0.363

AC:

9629

AN:

26532

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.366

Heterozygous variant carriers

7221

14442

21662

28883

36104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10156

20312

30468

40624

50780

<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:

0.402

AC:

58609

AN:

145738

Hom.:

12824

Cov.:

AF XY:

0.402

AC XY:

28543

AN XY:

70934

show subpopulations

African (AFR)

AF:

0.515

AC:

20092

AN:

38992

American (AMR)

AF:

0.481

AC:

6875

AN:

14304

Ashkenazi Jewish (ASJ)

AF:

0.630

AC:

2114

AN:

3356

East Asian (EAS)

AF:

0.331

AC:

1648

AN:

4986

South Asian (SAS)

AF:

0.393

AC:

1806

AN:

4592

European-Finnish (FIN)

AF:

0.315

AC:

3061

AN:

9730

Middle Eastern (MID)

AF:

0.469

AC:

134

AN:

286

European-Non Finnish (NFE)

AF:

0.323

AC:

21521

AN:

66600

Other (OTH)

AF:

0.459

AC:

921

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

1298

2596

3893

5191

6489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.358

Hom.:

37325

Asia WGS

AF:

0.382

AC:

1326

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.94

(source)

DANN

Benign

0.28

PhyloP100

-1.0

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over