rs244750

chr5-88851375-T-C

Variant summary

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

The NM_002397.5(MEF2C):c.-142-27445A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,064 control chromosomes in the GnomAD database, including 2,956 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 0.19 (2956 hom., cov: 31)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

Genes affected

MEF2C (HGNC:6996): (myocyte enhancer factor 2C) This locus encodes a member of the MADS box transcription enhancer factor 2 (MEF2) family of proteins, which play a role in myogenesis. The encoded protein, MEF2 polypeptide C, has both trans-activating and DNA binding activities. This protein may play a role in maintaining the differentiated state of muscle cells. Mutations and deletions at this locus have been associated with severe cognitive disability, stereotypic movements, epilepsy, and cerebral malformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2C	NM_002397.5	c.-142-27445A>G		intron_variant		ENST00000504921.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2C	ENST00000504921.7	c.-142-27445A>G		intron_variant		1	NM_002397.5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28841 AN: 151946 Hom.: 2950 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.190 AC: 28880 AN: 152064 Hom.: 2956 Cov.: 31 AF XY: 0.190 AC XY: 14116 AN XY: 74346

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0953

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.218

Alfa AF: 0.177 Hom.: 683

Bravo AF: 0.204

Asia WGS AF: 0.196 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.7
Dann	Benign	0.66

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: rs244750; hg19: chr5-88147192;