chr5-88776116-G-C

Variant names:

• chr5-88776116-G-C
• rs11744850
• NM_002397.5:c.259-14788C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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-AS2 (HGNC:53115): (MEF2C antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002397.5. 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_002397.5	MANE Select	c.259-14788C>G		intron	N/A	NP_002388.2
	MEF2C	NM_001193347.1		c.259-14788C>G		intron	N/A	NP_001180276.1	Q06413-5
	MEF2C	NM_001193350.2		c.259-14788C>G		intron	N/A	NP_001180279.1	Q06413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000504921.7	TSL:1 MANE Select	c.259-14788C>G		intron	N/A	ENSP00000421925.5	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.259-14788C>G		intron	N/A	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000437473.6	TSL:1	c.259-14788C>G		intron	N/A	ENSP00000396219.2	Q06413-1

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

African (AFR) AF: 0.219 AC: 9061 AN: 41362

American (AMR) AF: 0.447 AC: 6805 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2361 AN: 3466

East Asian (EAS) AF: 0.579 AC: 2996 AN: 5170

South Asian (SAS) AF: 0.625 AC: 3003 AN: 4804

European-Finnish (FIN) AF: 0.610 AC: 6399 AN: 10492

Middle Eastern (MID) AF: 0.566 AC: 164 AN: 290

European-Non Finnish (NFE) AF: 0.665 AC: 45162 AN: 67946

Other (OTH) AF: 0.534 AC: 1128 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.36
PhyloP100		-1.1
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: rs11744850; hg19: chr5-88071933;