NM_001319206.4:c.259-5693C>T

Variant names:

• chr15-99665630-C-T
• rs11247120
• NM_001319206.4:c.259-5693C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001319206.4(MEF2A):​c.259-5693C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 148,908 control chromosomes in the GnomAD database, including 14,781 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 (14781 hom., cov: 27)
• Consequence: MEF2A NM_001319206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.259-5693C>T		intron_variant	Intron 4 of 11	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.259-5693C>T		intron_variant	Intron 4 of 11	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 62705 AN: 148810 Hom.: 14767 Cov.: 27

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.421 AC: 62733 AN: 148908 Hom.: 14781 Cov.: 27 AF XY: 0.423 AC XY: 30675 AN XY: 72560

African (AFR) AF: 0.179 AC: 7142 AN: 39992

American (AMR) AF: 0.473 AC: 7031 AN: 14858

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1954 AN: 3462

East Asian (EAS) AF: 0.430 AC: 2160 AN: 5022

South Asian (SAS) AF: 0.541 AC: 2565 AN: 4742

European-Finnish (FIN) AF: 0.489 AC: 4859 AN: 9942

Middle Eastern (MID) AF: 0.617 AC: 179 AN: 290

European-Non Finnish (NFE) AF: 0.523 AC: 35357 AN: 67632

Other (OTH) AF: 0.469 AC: 967 AN: 2060

Alfa AF: 0.230 Hom.: 428

Bravo AF: 0.404

Asia WGS AF: 0.453 AC: 1575 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.76
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11247120; hg19: chr15-100205835;