15-99714520-T-C

Variant names:

• chr15-99714520-T-C
• rs897074
• NM_001319206.4:c.*1749T>C

Variant summary

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

The NM_001319206.4(MEF2A):​c.*1749T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,854 control chromosomes in the GnomAD database, including 13,941 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 0.42 (13941 hom., cov: 31)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: MEF2A NM_001319206.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.*1749T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.*1749T>C		3_prime_UTR_variant	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63651 AN: 151730 Hom.: 13897 Cov.: 31

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.420 AC: 63757 AN: 151850 Hom.: 13941 Cov.: 31 AF XY: 0.421 AC XY: 31245 AN XY: 74196

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.445

Alfa AF: 0.366 Hom.: 10654

Bravo AF: 0.424

Asia WGS AF: 0.483 AC: 1681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.28
DANN	Benign	0.61

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: rs897074; hg19: chr15-100254725;