chr15-99715609-A-T

Position:

• chr15-99715609-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.*2838A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,158 control chromosomes in the GnomAD database, including 49,634 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 0.80 (49630 hom., cov: 32)
  • Exomes 𝑓: 1.0 (4 hom.)
• Consequence: MEF2A NM_001319206.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.*2838A>T		3_prime_UTR_variant	12/12	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.*2838A>T		3_prime_UTR_variant	12/12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121901 AN: 152032 Hom.: 49590 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.826

GnomAD4 exome AF: 1.00 AC: 8 AN: 8 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 6 AN XY: 6

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.802 AC: 121996 AN: 152150 Hom.: 49630 Cov.: 32 AF XY: 0.804 AC XY: 59844 AN XY: 74388

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.924

Gnomad4 NFE AF: 0.861

Gnomad4 OTH AF: 0.828

Alfa AF: 0.824 Hom.: 6481

Bravo AF: 0.782

Asia WGS AF: 0.812 AC: 2825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.034
DANN	Benign	0.72

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: rs325381; hg19: chr15-100255814; COSMIC: COSV57537732; COSMIC: COSV57537732;