Genetic Variant MIAT:n.1467G>A (chr22-26666705-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000613780.4(MIAT):n.1467G>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 0.134 in 398,554 control chromosomes in the GnomAD database, including 3,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.14 ( 1665 hom., cov: 32)

Exomes 𝑓: 0.13 ( 2130 hom. )

Consequence

MIAT
ENST00000613780.4 non_coding_transcript_exon

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0440

Publications

22 publications found

Variant links:

Genes affected

MIAT (HGNC:33425): (myocardial infarction associated transcript) This gene encodes a spliced long non-coding RNA that may constitute a component of the nuclear matrix. Altered expression of this locus has been reported to be associated with a susceptibility to myocardial infarction. It has also been proposed that pathways involving this transcript may contribute to the pathophysiology of schizophrenia. A similar gene in mouse has been associated with retinal cell fate determination. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Dec 2014]

MIAT links:

MIATNB (HGNC:50731): (MIAT neighbor)

MIATNB links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 22-26666705-G-A is Benign according to our data. Variant chr22-26666705-G-A is described in ClinVar as Benign. ClinVar VariationId is 2691796.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MIAT	NR_003491.4 link	n.1399G>A	non_coding_transcript_exon_variant	Exon 3 of 5
MIAT	NR_033319.3 link	n.1399G>A	non_coding_transcript_exon_variant	Exon 3 of 4
MIAT	NR_033320.3 link	n.1325G>A	non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIAT	ENST00000613780.4 link	n.1467G>A	non_coding_transcript_exon_variant	Exon 3 of 5	1
MIAT	ENST00000616213.4 link	n.1393G>A	non_coding_transcript_exon_variant	Exon 3 of 4	1
MIAT	ENST00000616469.4 link	n.1519G>A	non_coding_transcript_exon_variant	Exon 3 of 4	1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21723

AN:

152076

Hom.:

1661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.0951

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0820

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.129

AC:

31742

AN:

246360

Hom.:

2130

Cov.:

AF XY:

0.130

AC XY:

16198

AN XY:

124840

show subpopulations

African (AFR)

AF:

0.179

AC:

1284

AN:

7182

American (AMR)

AF:

0.0817

AC:

607

AN:

7434

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

1109

AN:

9242

East Asian (EAS)

AF:

0.0707

AC:

1620

AN:

22898

South Asian (SAS)

AF:

0.0818

AC:

248

AN:

3032

European-Finnish (FIN)

AF:

0.157

AC:

3262

AN:

20824

Middle Eastern (MID)

AF:

0.138

AC:

179

AN:

1294

European-Non Finnish (NFE)

AF:

0.134

AC:

21194

AN:

158078

Other (OTH)

AF:

0.137

AC:

2239

AN:

16376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

2074

4148

6222

8296

10370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.143

AC:

21744

AN:

152194

Hom.:

1665

Cov.:

AF XY:

0.143

AC XY:

10650

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.184

AC:

7619

AN:

41498

American (AMR)

AF:

0.0948

AC:

1450

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

460

AN:

3472

East Asian (EAS)

AF:

0.102

AC:

531

AN:

5184

South Asian (SAS)

AF:

0.0827

AC:

399

AN:

4826

European-Finnish (FIN)

AF:

0.158

AC:

1672

AN:

10596

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9070

AN:

68006

Other (OTH)

AF:

0.124

AC:

262

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

912

1824

2736

3648

4560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.134

Hom.:

941

Bravo

AF:

0.141

Asia WGS

AF:

0.0880

AC:

305

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MIAT-related disorder

Benign:1

Jan 28, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

(source)

DANN

Benign

0.68

PhyloP100

0.044

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over