rs1164925540

Variant names:

• chr5-88883309-GAGGAGGAGGAAGA-G
• rs1164925540
• ENST00000437473.6:c.-507_-495delTCTTCCTCCTCCT

Your query was ambiguous. Multiple possible variants found:

• chr5-88883309-GAGGAGGAGGAAGA-G
• chr5-88883309-GAGGAGGAGGAAGA-GAGGAGGAGGAAGAAGGAGGAGGAAGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000437473.6(MEF2C):​c.-507_-495delTCTTCCTCCTCCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 151,878 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEF2C ENST00000437473.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.71
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 5-88883309-GAGGAGGAGGAAGA-G is Benign according to our data. Variant chr5-88883309-GAGGAGGAGGAAGA-G is described in ClinVar as Benign. ClinVar VariationId is 1695134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00201 (305/151878) while in subpopulation NFE AF = 0.00356 (242/67916). AF 95% confidence interval is 0.00319. There are 1 homozygotes in GnomAd4. There are 130 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High AC in GnomAd4 at 305 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437473.6. 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.-143+4180_-143+4192delTCTTCCTCCTCCT		intron	N/A	NP_001180276.1	Q06413-5
	MEF2C	NM_001364329.2		c.-140+4180_-140+4192delTCTTCCTCCTCCT		intron	N/A	NP_001351258.1	Q06413-1
	MEF2C	NM_001364330.2		c.-143+4180_-143+4192delTCTTCCTCCTCCT		intron	N/A	NP_001351259.1	Q06413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000437473.6	TSL:1	c.-507_-495delTCTTCCTCCTCCT		5_prime_UTR	Exon 1 of 11	ENSP00000396219.2	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.-143+4180_-143+4192delTCTTCCTCCTCCT		intron	N/A	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000424173.6	TSL:1	c.-143+4180_-143+4192delTCTTCCTCCTCCT		intron	N/A	ENSP00000389610.2	Q06413-6

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 305 AN: 151770 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000722

Gnomad ASJ AF: 0.000867

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00171

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00356

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1608 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1082

African (AFR) AF: 0.00 AC: 0 AN: 18

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 52

South Asian (SAS) AF: 0.00 AC: 0 AN: 572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842

Other (OTH) AF: 0.00 AC: 0 AN: 74

GnomAD4 genome AF: 0.00201 AC: 305 AN: 151878 Hom.: 1 Cov.: 27 AF XY: 0.00175 AC XY: 130 AN XY: 74234

African (AFR) AF: 0.000724 AC: 30 AN: 41446

American (AMR) AF: 0.000721 AC: 11 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000867 AC: 3 AN: 3462

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00171 AC: 18 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00356 AC: 242 AN: 67916

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.000919 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MEF2C-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1164925540; hg19: chr5-88179126;