rs8029326

Positions:

• chr15-99655247-G-A

Variant summary

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

The NM_001319206.4(MEF2A):​c.258+9483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,972 control chromosomes in the GnomAD database, including 10,652 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 0.34 (10652 hom., cov: 32)
• Consequence: MEF2A NM_001319206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2A	NM_001319206.4	c.258+9483G>A		intron_variant		ENST00000557942.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2A	ENST00000557942.6	c.258+9483G>A		intron_variant		5	NM_001319206.4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51223 AN: 151854 Hom.: 10648 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.369

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.337 AC: 51220 AN: 151972 Hom.: 10652 Cov.: 32 AF XY: 0.338 AC XY: 25109 AN XY: 74278

Gnomad4 AFR AF: 0.0830

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.367

Alfa AF: 0.428 Hom.: 6680

Bravo AF: 0.324

Asia WGS AF: 0.340 AC: 1182 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.26

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: rs8029326; hg19: chr15-100195452;