Variant 15-99706731-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001319206.4(MEF2A):c.885T>C(p.Asn295=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,611,158 control chromosomes in the GnomAD database, including 482,743 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.65 ( 35909 hom., cov: 31)

Exomes 𝑓: 0.78 ( 446834 hom. )

Consequence

MEF2A
NM_001319206.4 splice_region, synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.353

Variant links:

Genes affected

MEF2A (HGNC:6993): (myocyte enhancer factor 2A) The protein encoded by this gene is a DNA-binding transcription factor that activates many muscle-specific, growth factor-induced, and stress-induced genes. The encoded protein can act as a homodimer or as a heterodimer and is involved in several cellular processes, including muscle development, neuronal differentiation, cell growth control, and apoptosis. Defects in this gene could be a cause of autosomal dominant coronary artery disease 1 with myocardial infarction (ADCAD1). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

MEF2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 15-99706731-T-C is Benign according to our data. Variant chr15-99706731-T-C is described in ClinVar as [Benign]. Clinvar id is 3058865.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.353 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2A	NM_001319206.4 linkuse as main transcript	c.885T>C	p.Asn295=	splice_region_variant, synonymous_variant	10/12	ENST00000557942.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2A	ENST00000557942.6 linkuse as main transcript	c.885T>C	p.Asn295=	splice_region_variant, synonymous_variant	10/12	5	NM_001319206.4		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98568

AN:

152008

Hom.:

35887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.936

Gnomad AMR

AF:

0.680

Gnomad ASJ

AF:

0.848

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.847

Gnomad FIN

AF:

0.836

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.792

Gnomad OTH

AF:

0.702

GnomAD3 exomes

AF:

0.752

AC:

187356

AN:

249158

Hom.:

72751

AF XY:

0.769

AC XY:

103882

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.669

Gnomad ASJ exome

AF:

0.859

Gnomad EAS exome

AF:

0.733

Gnomad SAS exome

AF:

0.848

Gnomad FIN exome

AF:

0.824

Gnomad NFE exome

AF:

0.794

Gnomad OTH exome

AF:

0.783

GnomAD4 exome

AF:

0.778

AC:

1134689

AN:

1459032

Hom.:

446834

Cov.:

AF XY:

0.782

AC XY:

568024

AN XY:

725950

show subpopulations

Gnomad4 AFR exome

AF:

0.279

Gnomad4 AMR exome

AF:

0.671

Gnomad4 ASJ exome

AF:

0.861

Gnomad4 EAS exome

AF:

0.795

Gnomad4 SAS exome

AF:

0.849

Gnomad4 FIN exome

AF:

0.820

Gnomad4 NFE exome

AF:

0.787

Gnomad4 OTH exome

AF:

0.769

GnomAD4 genome

AF:

0.648

AC:

98631

AN:

152126

Hom.:

35909

Cov.:

AF XY:

0.656

AC XY:

48768

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.680

Gnomad4 ASJ

AF:

0.848

Gnomad4 EAS

AF:

0.745

Gnomad4 SAS

AF:

0.846

Gnomad4 FIN

AF:

0.836

Gnomad4 NFE

AF:

0.792

Gnomad4 OTH

AF:

0.705

Alfa

AF:

0.732

Hom.:

29500

Bravo

AF:

0.620

Asia WGS

AF:

0.775

AC:

2692

AN:

3478

EpiCase

AF:

0.799

EpiControl

AF:

0.799

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MEF2A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.6

DANN

Benign

0.75

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

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