dbSNP rs17560407: MEF2C:c.-239-236T>C (chr5-88887834-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001193347.1(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
NM_001193347.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.677

Publications

9 publications found

Variant links:

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 links:

MEF2C-AS1 (HGNC:48908): (MEF2C antisense RNA 1)

MEF2C-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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: NM_001193347.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
MEF2C	NM_001193347.1	c.-239-236T>C	intron	N/A	NP_001180276.1	Q06413-5
MEF2C	NM_001364329.2	c.-236-236T>C	intron	N/A	NP_001351258.1	Q06413-1
MEF2C	NM_001364330.2	c.-239-236T>C	intron	N/A	NP_001351259.1	Q06413-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MEF2C	ENST00000340208.9	TSL:1	c.-239-236T>C	intron	N/A	ENSP00000340874.5	Q06413-5
MEF2C	ENST00000424173.6	TSL:1	c.-239-236T>C	intron	N/A	ENSP00000389610.2	Q06413-6
MEF2C	ENST00000944376.1		c.-239-236T>C	intron	N/A	ENSP00000614435.1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28181

AN:

152116

Hom.:

2856

Cov.:

show subpopulations

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.:

AF XY:

0.182

AC XY:

13581

AN XY:

74428

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16057

AN:

68002

Other (OTH)

AF:

0.196

AC:

413

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1162

2324

3486

4648

5810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.171

Hom.:

1122

Bravo

AF:

0.177

Asia WGS

AF:

0.186

AC:

645

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.0

(source)

DANN

Benign

0.77

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over