chr5-88856300-C-T

Position:

• chr5-88856300-C-T

Variant summary

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

The ENST00000504921.7(MEF2C):​c.-143+26655G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,198 control chromosomes in the GnomAD database, including 51,783 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 0.82 (51783 hom., cov: 32)
• Consequence: MEF2C ENST00000504921.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.-143+26655G>A		intron_variant		ENST00000504921.7	NP_002388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000504921.7	c.-143+26655G>A		intron_variant		1	NM_002397.5	ENSP00000421925

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125058 AN: 152080 Hom.: 51726 Cov.: 32

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.822 AC: 125173 AN: 152198 Hom.: 51783 Cov.: 32 AF XY: 0.823 AC XY: 61258 AN XY: 74404

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.814

Alfa AF: 0.773 Hom.: 4657

Bravo AF: 0.829

Asia WGS AF: 0.818 AC: 2847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.45

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: rs700585; hg19: chr5-88152117;