rs4521516

Positions:

• chr5-88804134-G-C

Variant summary

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

The NM_002397.5(MEF2C):​c.258+464C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,146 control chromosomes in the GnomAD database, including 1,812 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 0.15 (1812 hom., cov: 32)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2C	NM_002397.5	c.258+464C>G		intron_variant		ENST00000504921.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2C	ENST00000504921.7	c.258+464C>G		intron_variant		1	NM_002397.5

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22424 AN: 152028 Hom.: 1816 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.147 AC: 22426 AN: 152146 Hom.: 1812 Cov.: 32 AF XY: 0.150 AC XY: 11135 AN XY: 74378

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0721

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.133

Alfa AF: 0.134 Hom.: 203

Bravo AF: 0.152

Asia WGS AF: 0.215 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.51

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: rs4521516; hg19: chr5-88099951;