rs17560407

Variant names:

• chr5-88887834-A-G
• rs17560407
• ENST00000340208.9:c.-239-236T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-88887834-A-G
• chr5-88887834-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000340208.9(MEF2C):​c.-239-236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,234 control chromosomes in the GnomAD database, including 2,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (2861 hom., cov: 33)
• Consequence: MEF2C ENST00000340208.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.677
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-88887834-A-G is Benign according to our data. Variant chr5-88887834-A-G is described in ClinVar as Benign. ClinVar VariationId is 1249101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000340208.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	NM_001193347.1		c.-239-236T>C		intron	N/A	NP_001180276.1
	MEF2C	NM_001364329.2		c.-236-236T>C		intron	N/A	NP_001351258.1
	MEF2C	NM_001364330.2		c.-239-236T>C		intron	N/A	NP_001351259.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000340208.9	TSL:1	c.-239-236T>C		intron	N/A	ENSP00000340874.5
	MEF2C	ENST00000424173.6	TSL:1	c.-239-236T>C		intron	N/A	ENSP00000389610.2
	MEF2C	ENST00000629612.2	TSL:5	c.-236-236T>C		intron	N/A	ENSP00000486554.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28181 AN: 152116 Hom.: 2856 Cov.: 33

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.185 AC: 28179 AN: 152234 Hom.: 2861 Cov.: 33 AF XY: 0.182 AC XY: 13581 AN XY: 74428

African (AFR) AF: 0.0969 AC: 4029 AN: 41562

American (AMR) AF: 0.176 AC: 2696 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1105 AN: 5178

South Asian (SAS) AF: 0.195 AC: 941 AN: 4832

European-Finnish (FIN) AF: 0.204 AC: 2154 AN: 10582

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16057 AN: 68002

Other (OTH) AF: 0.196 AC: 413 AN: 2110

Alfa AF: 0.171 Hom.: 1122

Bravo AF: 0.177

Asia WGS AF: 0.186 AC: 645 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.77
PhyloP100		0.68
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: rs17560407; hg19: chr5-88183651;