chr5-88891137-A-G

Variant names:

• chr5-88891137-A-G
• rs3850653
• ENST00000340208.9:c.-239-3539T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193347.1(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 NM_001193347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193347.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	NM_001193347.1		c.-239-3539T>C		intron	N/A	NP_001180276.1	Q06413-5
	MEF2C	NM_001131005.2		c.-239-3539T>C		intron	N/A	NP_001124477.1	Q06413-6
	MEF2C-AS1	NR_104031.1		n.173+1657A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000340208.9	TSL:1	c.-239-3539T>C		intron	N/A	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000424173.6	TSL:1	c.-239-3539T>C		intron	N/A	ENSP00000389610.2	Q06413-6
	MEF2C-AS1	ENST00000514011.6	TSL:1	n.197+1657A>G		intron	N/A

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

African (AFR) AF: 0.0888 AC: 3690 AN: 41554

American (AMR) AF: 0.175 AC: 2681 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3472

East Asian (EAS) AF: 0.203 AC: 1051 AN: 5190

South Asian (SAS) AF: 0.197 AC: 949 AN: 4826

European-Finnish (FIN) AF: 0.203 AC: 2145 AN: 10556

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15967 AN: 67982

Other (OTH) AF: 0.194 AC: 409 AN: 2112

Alfa AF: 0.212 Hom.: 2997

Bravo AF: 0.173

Asia WGS AF: 0.184 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.8
DANN	Benign	0.89
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3850653; hg19: chr5-88186954;