rs3850653

chr5-88891137-A-G

Variant summary

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

The ENST00000340208.9(MEF2C):c.-239-3539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,174 control chromosomes in the GnomAD database, including 2,778 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 0.18 (2778 hom., cov: 32)
• Consequence: MEF2C ENST00000340208.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486

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-AS1 (HGNC:48908): (MEF2C antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2C-AS1	NR_136218.1	n.156+7652A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2C-AS1	ENST00000514092.5	n.36+1657A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27657 AN: 152056 Hom.: 2773 Cov.: 32

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.182 AC: 27657 AN: 152174 Hom.: 2778 Cov.: 32 AF XY: 0.179 AC XY: 13348 AN XY: 74394

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.194

Alfa AF: 0.214 Hom.: 2236

Bravo AF: 0.173

Asia WGS AF: 0.184 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	4.8
Dann	Benign	0.89

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: rs3850653; hg19: chr5-88186954;