5-88883337-AAGGAGGAGG-AAGG

Variant names:

• chr5-88883337-AAGGAGG-A
• rs567979916
• ENST00000437473.6:c.-528_-523delCCTCCT

Variant summary

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

The ENST00000437473.6(MEF2C):​c.-528_-523delCCTCCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000945 in 150,194 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 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:1
• Conservation: PhyloP100: 1.38
• 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 5-88883337-AAGGAGG-A is Benign according to our data. Variant chr5-88883337-AAGGAGG-A is described in ClinVar as Benign. ClinVar VariationId is 2655583.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000945 (142/150194) while in subpopulation AFR AF = 0.00274 (112/40870). AF 95% confidence interval is 0.00233. There are 0 homozygotes in GnomAd4. There are 61 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High AC in GnomAd4 at 142 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+4159_-143+4164delCCTCCT		intron	N/A	NP_001180276.1	Q06413-5
	MEF2C	NM_001364329.2		c.-140+4159_-140+4164delCCTCCT		intron	N/A	NP_001351258.1	Q06413-1
	MEF2C	NM_001364330.2		c.-143+4159_-143+4164delCCTCCT		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.-528_-523delCCTCCT		5_prime_UTR	Exon 1 of 11	ENSP00000396219.2	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.-143+4159_-143+4164delCCTCCT		intron	N/A	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000424173.6	TSL:1	c.-143+4159_-143+4164delCCTCCT		intron	N/A	ENSP00000389610.2	Q06413-6

Frequencies

GnomAD3 genomes AF: 0.000953 AC: 143 AN: 150096 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000398

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000311

Gnomad OTH AF: 0.000973

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1428 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 916

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

American (AMR) AF: 0.00 AC: 0 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 30

South Asian (SAS) AF: 0.00 AC: 0 AN: 546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 56

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 22

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 674

Other (OTH) AF: 0.00 AC: 0 AN: 56

GnomAD4 genome AF: 0.000945 AC: 142 AN: 150194 Hom.: 0 Cov.: 27 AF XY: 0.000831 AC XY: 61 AN XY: 73406

African (AFR) AF: 0.00274 AC: 112 AN: 40870

American (AMR) AF: 0.000397 AC: 6 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5062

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000312 AC: 21 AN: 67412

Other (OTH) AF: 0.000962 AC: 2 AN: 2078

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

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
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs567979916; hg19: chr5-88179154;