rs325380

Positions:

• chr15-99716413-A-C
• chr15-99716413-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.90

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]

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MEF2A	NM_001319206.4	c.*3642A>C		3_prime_UTR_variant	12/12	ENST00000557942.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2A	ENST00000557942.6	c.*3642A>C		3_prime_UTR_variant	12/12	5	NM_001319206.4

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65919 AN: 151996 Hom.: 16873 Cov.: 33

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

GnomAD3 exomes AF: 0.510 AC: 66764 AN: 130936 Hom.: 18042 AF XY: 0.518 AC XY: 36923 AN XY: 71260

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 SAS exome AF: 0.530

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.: 0 AF XY: 0.535 AC XY: 81806 AN XY: 152982

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.487

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.527

GnomAD4 genome AF: 0.433 AC: 65920 AN: 152114 Hom.: 16876 Cov.: 33 AF XY: 0.433 AC XY: 32164 AN XY: 74354

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.458

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	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Uncertain	0.97
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.00042	T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0e-37	P;P;P;P
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.57
Vest4		0.046
ClinPred		0.082	T
GERP RS		5.9

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

Other links and lift over

dbSNP: rs325380; hg19: chr15-100256618; COSMIC: COSV57529974; COSMIC: COSV57529974;