Variant 5-88887496-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001193347.1(MEF2C):c.-143+6T>C variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00025 in 152,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

MEF2C
NM_001193347.1 splice_region, intron

Scores

Splicing: ADA: 0.9927

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.35

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 5-88887496-A-G is Benign according to our data. Variant chr5-88887496-A-G is described in ClinVar as [Benign]. Clinvar id is 1234212.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00025 (38/152134) while in subpopulation NFE AF= 0.000441 (30/68006). AF 95% confidence interval is 0.000317. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
MEF2C	NM_001193347.1 link	c.-143+6T>C	splice_region_variant, intron_variant	NP_001180276.1	Q06413-5
MEF2C	NM_001364329.2 link	c.-140+6T>C	splice_region_variant, intron_variant	NP_001351258.1
MEF2C	NM_001364330.2 link	c.-143+6T>C	splice_region_variant, intron_variant	NP_001351259.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
MEF2C	ENST00000340208.9 link	c.-143+6T>C	splice_region_variant, intron_variant	1	ENSP00000340874.5	Q06413-5
MEF2C	ENST00000424173.6 link	c.-143+6T>C	splice_region_variant, intron_variant	1	ENSP00000389610.2	Q06413-6
MEF2C	ENST00000629612.2 link	c.-140+6T>C	splice_region_variant, intron_variant	5	ENSP00000486554.1	Q06413-2

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.000250

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000479

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.82

SpliceAI score (max)

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over