rs9293505

Variant names:

• chr5-88890652-G-T
• rs9293505
• ENST00000340208.9:c.-239-3054C>A

Variant summary

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

The NM_001193347.1(MEF2C):​c.-239-3054C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 152,084 control chromosomes in the GnomAD database, including 874 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 0.074 (874 hom., cov: 32)
• Consequence: MEF2C NM_001193347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2C	NM_001193347.1	c.-239-3054C>A		intron_variant	Intron 1 of 11		NP_001180276.1
MEF2C	NM_001131005.2	c.-239-3054C>A		intron_variant	Intron 1 of 10		NP_001124477.1
MEF2C	XM_011543396.4	c.-239-3054C>A		intron_variant	Intron 1 of 11		XP_011541698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000340208.9	c.-239-3054C>A		intron_variant	Intron 1 of 11	1		ENSP00000340874.5
MEF2C	ENST00000424173.6	c.-239-3054C>A		intron_variant	Intron 1 of 10	1		ENSP00000389610.2
MEF2C-AS1	ENST00000514011.5	n.146+1172G>T		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11171 AN: 151966 Hom.: 868 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0154

Gnomad FIN AF: 0.00897

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0737 AC: 11205 AN: 152084 Hom.: 874 Cov.: 32 AF XY: 0.0721 AC XY: 5362 AN XY: 74350

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0575

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0150

Gnomad4 FIN AF: 0.00897

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0276 Hom.: 305

Bravo AF: 0.0831

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.5
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9293505; hg19: chr5-88186469;