rs160044

Positions:

• chr5-88818659-T-C
• chr5-88818659-T-G

Variant summary

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

The NM_002397.5(MEF2C):​c.54+5076A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,758 control chromosomes in the GnomAD database, including 15,728 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 0.43 (15728 hom., cov: 32)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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 (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.54+5076A>G		intron_variant		ENST00000504921.7	NP_002388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000504921.7	c.54+5076A>G		intron_variant		1	NM_002397.5	ENSP00000421925

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64458 AN: 151640 Hom.: 15691 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.425 AC: 64549 AN: 151758 Hom.: 15728 Cov.: 32 AF XY: 0.421 AC XY: 31255 AN XY: 74154

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.424

Alfa AF: 0.331 Hom.: 17410

Bravo AF: 0.455

Asia WGS AF: 0.403 AC: 1402 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	3.3
DANN	Benign	0.64

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: rs160044; hg19: chr5-88114476;