5-88776116-G-C

Position:

• chr5-88776116-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.259-14788C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,790 control chromosomes in the GnomAD database, including 22,798 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 0.51 (22798 hom., cov: 32)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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]

MEF2C-AS2 (HGNC:53115): (MEF2C antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2C	NM_002397.5	c.259-14788C>G		intron_variant		ENST00000504921.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2C	ENST00000504921.7	c.259-14788C>G		intron_variant		1	NM_002397.5
MEF2C-AS2	ENST00000657578.1	n.292-2630G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77625 AN: 151672 Hom.: 22803 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.511 AC: 77635 AN: 151790 Hom.: 22798 Cov.: 32 AF XY: 0.514 AC XY: 38172 AN XY: 74218

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.534

Alfa AF: 0.456 Hom.: 1522

Bravo AF: 0.478

Asia WGS AF: 0.559 AC: 1930 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.36

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: rs11744850; hg19: chr5-88071933;