Genetic Variant MEF2A:c.*3642A>C (chr15-99716413-A-C) – 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.*3642A>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.497 in 426,464 control chromosomes in the GnomAD database, including 57,026 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 ( 16876 hom., cov: 33)

Exomes 𝑓: 0.53 ( 40150 hom. )

Consequence

MEF2A
NM_001319206.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.90

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:

LYSMD4 (HGNC:26571): (LysM domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LYSMD4 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 (MetaRNN=4.2113662E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4 link	c.*3642A>C		3_prime_UTR_variant	Exon 12 of 12	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.*3642A>C		3_prime_UTR_variant	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65919

AN:

151996

Hom.:

16873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.565

Gnomad OTH

AF:

0.461

GnomAD2 exomes

AF:

0.510

AC:

66764

AN:

130936

AF XY:

0.518

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.622

Gnomad EAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.571

Gnomad NFE exome

AF:

0.565

Gnomad OTH exome

AF:

0.527

GnomAD4 exome

AF:

0.532

AC:

146070

AN:

274350

Hom.:

40150

Cov.:

AF XY:

0.535

AC XY:

81806

AN XY:

152982

show subpopulations

Gnomad4 AFR exome

AF:

0.145

AC:

1107

AN:

7656

Gnomad4 AMR exome

AF:

0.487

AC:

11858

AN:

24330

Gnomad4 ASJ exome

AF:

0.615

AC:

6126

AN:

9964

Gnomad4 EAS exome

AF:

0.340

AC:

2900

AN:

8536

Gnomad4 SAS exome

AF:

0.535

AC:

31003

AN:

57958

Gnomad4 FIN exome

AF:

0.571

AC:

7125

AN:

12476

Gnomad4 NFE exome

AF:

0.564

AC:

77851

AN:

138016

Gnomad4 Remaining exome

AF:

0.527

AC:

6717

AN:

12754

Heterozygous variant carriers

3225

6450

9675

12900

16125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.433

AC:

65920

AN:

152114

Hom.:

16876

Cov.:

AF XY:

0.433

AC XY:

32164

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.148

AC:

0.14836

AN:

0.14836

Gnomad4 AMR

AF:

0.465

AC:

0.46501

AN:

0.46501

Gnomad4 ASJ

AF:

0.623

AC:

0.623055

AN:

0.623055

Gnomad4 EAS

AF:

0.345

AC:

0.344621

AN:

0.344621

Gnomad4 SAS

AF:

0.524

AC:

0.524274

AN:

0.524274

Gnomad4 FIN

AF:

0.570

AC:

0.569871

AN:

0.569871

Gnomad4 NFE

AF:

0.565

AC:

0.565455

AN:

0.565455

Gnomad4 OTH

AF:

0.458

AC:

0.45786

AN:

0.45786

Heterozygous variant carriers

1684

3367

5051

6734

8418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.466

Hom.:

5429

Bravo

AF:

0.413

TwinsUK

AF:

0.557

AC:

2066

ALSPAC

AF:

0.560

AC:

2160

ExAC

AF:

0.499

AC:

8836

Asia WGS

AF:

0.401

AC:

1394

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.97

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.33

MetaRNN

Benign

0.00042

MetaSVM

Benign

-0.89

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.57

Vest4

0.046

ClinPred

0.082

GERP RS

5.9

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over