Genetic Variant ENST00000606743.1:n.689T>C (chr6-31394807-A-G) – 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.689T>C 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 0.321 in 129,462 control chromosomes in the GnomAD database, including 8,663 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 0.34 ( 8623 hom., cov: 24)

Exomes 𝑓: 0.084 ( 40 hom. )

Consequence

MICA-AS1
ENST00000606743.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.488

Publications

2 publications found

Variant links:

COSMIC-nc: COSV74094083

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

new If you want to explore the variant's impact on the transcript ENST00000606743.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.98).

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000606743.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA-AS1	NR_148222.1		n.828T>C		non_coding_transcript_exon	Exon 2 of 2
	MICA-AS1	NR_148223.1		n.861T>C		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
MICA-AS1	ENST00000606743.1	TSL:6	n.689T>C	non_coding_transcript_exon	Exon 1 of 1
MICA-AS1	ENST00000745010.1		n.1151T>C	non_coding_transcript_exon	Exon 2 of 2
MICA-AS1	ENST00000745011.1		n.1088T>C	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

40730

AN:

120060

Hom.:

8601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.575

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.399

GnomAD4 exome

AF:

0.0840

AC:

782

AN:

9312

Hom.:

Cov.:

AF XY:

0.0835

AC XY:

376

AN XY:

4504

show subpopulations

African (AFR)

AF:

0.194

AC:

AN:

108

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0455

AC:

AN:

East Asian (EAS)

AF:

0.0789

AC:

AN:

South Asian (SAS)

AF:

0.112

AC:

AN:

116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0831

AC:

723

AN:

8704

Other (OTH)

AF:

0.0638

AC:

AN:

298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.339

AC:

40790

AN:

120150

Hom.:

8623

Cov.:

AF XY:

0.335

AC XY:

19441

AN XY:

58054

show subpopulations

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

African (AFR)

AF:

0.460

AC:

14343

AN:

31192

American (AMR)

AF:

0.417

AC:

4770

AN:

11442

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

1383

AN:

2406

East Asian (EAS)

AF:

0.243

AC:

961

AN:

3954

South Asian (SAS)

AF:

0.319

AC:

1198

AN:

3754

European-Finnish (FIN)

AF:

0.216

AC:

1646

AN:

7638

Middle Eastern (MID)

AF:

0.405

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.270

AC:

15463

AN:

57220

Other (OTH)

AF:

0.400

AC:

672

AN:

1678

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.368

Heterozygous variant carriers

1118

2236

3354

4472

5590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.352

Hom.:

1328

Asia WGS

AF:

0.376

AC:

1306

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

3.6

(source)

DANN

Benign

0.66

PhyloP100

-0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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