Genetic Variant MEF2A:c.610+141A>T (chr15-99674753-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001319206.4(MEF2A):c.610+141A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 721,086 control chromosomes in the GnomAD database, including 87,851 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 0.43 ( 15052 hom., cov: 32)

Exomes 𝑓: 0.50 ( 72799 hom. )

Consequence

MEF2A
NM_001319206.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.494

Publications

8 publications found

Variant links:

Genes affected

MEF2A (HGNC:6993): (myocyte enhancer factor 2A) The protein encoded by this gene is a DNA-binding transcription factor that activates many muscle-specific, growth factor-induced, and stress-induced genes. The encoded protein can act as a homodimer or as a heterodimer and is involved in several cellular processes, including muscle development, neuronal differentiation, cell growth control, and apoptosis. Defects in this gene could be a cause of autosomal dominant coronary artery disease 1 with myocardial infarction (ADCAD1). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

MEF2A links:

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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=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4 link	c.610+141A>T		intron_variant	Intron 6 of 11	ENST00000557942.6	NP_001306135.1	Q02078-2A0A0S2Z4N0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6 link	c.610+141A>T		intron_variant	Intron 6 of 11	5	NM_001319206.4	ENSP00000453095.1		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64703

AN:

151962

Hom.:

15041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.472

GnomAD4 exome

AF:

0.501

AC:

285013

AN:

569006

Hom.:

72799

AF XY:

0.505

AC XY:

149369

AN XY:

295800

show subpopulations

African (AFR)

AF:

0.228

AC:

3389

AN:

14842

American (AMR)

AF:

0.477

AC:

9641

AN:

20230

Ashkenazi Jewish (ASJ)

AF:

0.586

AC:

8582

AN:

14644

East Asian (EAS)

AF:

0.462

AC:

14868

AN:

32148

South Asian (SAS)

AF:

0.527

AC:

24564

AN:

46596

European-Finnish (FIN)

AF:

0.464

AC:

14753

AN:

31820

Middle Eastern (MID)

AF:

0.572

AC:

1356

AN:

2370

European-Non Finnish (NFE)

AF:

0.512

AC:

192850

AN:

376306

Other (OTH)

AF:

0.500

AC:

15010

AN:

30050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6743

13486

20229

26972

33715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2670

5340

8010

10680

13350

<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:

0.426

AC:

64734

AN:

152080

Hom.:

15052

Cov.:

AF XY:

0.425

AC XY:

31623

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.223

AC:

9252

AN:

41478

American (AMR)

AF:

0.461

AC:

7039

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1961

AN:

3470

East Asian (EAS)

AF:

0.426

AC:

2201

AN:

5172

South Asian (SAS)

AF:

0.535

AC:

2579

AN:

4818

European-Finnish (FIN)

AF:

0.457

AC:

4828

AN:

10560

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.518

AC:

35182

AN:

67980

Other (OTH)

AF:

0.470

AC:

992

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1799

3597

5396

7194

8993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.467

Hom.:

2167

Bravo

AF:

0.418

Asia WGS

AF:

0.459

AC:

1595

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.6

(source)

DANN

Benign

0.74

PhyloP100

0.49

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