15-99674753-A-T

Position:

• chr15-99674753-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.610+141A>T		intron_variant		ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.610+141A>T		intron_variant		5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64703 AN: 151962 Hom.: 15041 Cov.: 32

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

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.586

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.527

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.512

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.426 AC: 64734 AN: 152080 Hom.: 15052 Cov.: 32 AF XY: 0.425 AC XY: 31623 AN XY: 74354

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.470

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
DANN	Benign	0.74

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: rs2033547; hg19: chr15-100214958;