rs770189

Positions:

• chr5-88792622-G-C
• chr5-88792622-G-T

Variant summary

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

The NM_002397.5(MEF2C):​c.258+11976C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,038 control chromosomes in the GnomAD database, including 27,634 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 0.58 (27634 hom., cov: 32)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2C	NM_002397.5	c.258+11976C>G		intron_variant		ENST00000504921.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2C	ENST00000504921.7	c.258+11976C>G		intron_variant		1	NM_002397.5

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88758 AN: 151918 Hom.: 27632 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.584 AC: 88792 AN: 152038 Hom.: 27634 Cov.: 32 AF XY: 0.584 AC XY: 43428 AN XY: 74322

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.593

Alfa AF: 0.673 Hom.: 19194

Bravo AF: 0.555

Asia WGS AF: 0.571 AC: 1987 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.39

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: rs770189; hg19: chr5-88088439;