rs34851361

Variant names:

• chr15-99712687-A-G
• rs34851361
• NM_001319206.4:c.1434A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001319206.4(MEF2A):​c.1434A>G​(p.Pro478Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 1,561,912 control chromosomes in the GnomAD database, including 6,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.063 (428 hom., cov: 32)
  • Exomes 𝑓: 0.087 (5823 hom.)
• Consequence: MEF2A NM_001319206.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.14
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 15-99712687-A-G is Benign according to our data. Variant chr15-99712687-A-G is described in ClinVar as Benign. ClinVar VariationId is 3056661.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319206.4. 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
	MEF2A	NM_001319206.4	MANE Select	c.1434A>G	p.Pro478Pro	synonymous	Exon 12 of 12	NP_001306135.1	Q02078-2
	MEF2A	NM_001400028.1		c.1548A>G	p.Pro516Pro	synonymous	Exon 12 of 12	NP_001386957.1
	MEF2A	NM_001365201.3		c.1452A>G	p.Pro484Pro	synonymous	Exon 12 of 12	NP_001352130.1	A0A8I5KVQ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2A	ENST00000557942.6	TSL:5 MANE Select	c.1434A>G	p.Pro478Pro	synonymous	Exon 12 of 12	ENSP00000453095.1	Q02078-2
	MEF2A	ENST00000354410.9	TSL:1	c.1416A>G	p.Pro472Pro	synonymous	Exon 11 of 11	ENSP00000346389.5	Q02078-5
	MEF2A	ENST00000947006.1		c.1572A>G	p.Pro524Pro	synonymous	Exon 12 of 12	ENSP00000617065.1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9579 AN: 151940 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0268

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.0724

GnomAD2 exomes AF: 0.0615 AC: 10754 AN: 174956 AF XY: 0.0614

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.0451

Gnomad ASJ exome AF: 0.0896

Gnomad EAS exome AF: 0.0000816

Gnomad FIN exome AF: 0.0474

Gnomad NFE exome AF: 0.0931

Gnomad OTH exome AF: 0.0751

GnomAD4 exome AF: 0.0865 AC: 121964 AN: 1409854 Hom.: 5823 Cov.: 38 AF XY: 0.0845 AC XY: 58846 AN XY: 696290

African (AFR) AF: 0.0225 AC: 720 AN: 32050

American (AMR) AF: 0.0480 AC: 1776 AN: 36966

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 2237 AN: 25294

East Asian (EAS) AF: 0.000191 AC: 7 AN: 36568

South Asian (SAS) AF: 0.0298 AC: 2375 AN: 79668

European-Finnish (FIN) AF: 0.0499 AC: 2495 AN: 50044

Middle Eastern (MID) AF: 0.0914 AC: 522 AN: 5712

European-Non Finnish (NFE) AF: 0.0987 AC: 107074 AN: 1084954

Other (OTH) AF: 0.0812 AC: 4758 AN: 58598

GnomAD4 genome AF: 0.0630 AC: 9578 AN: 152058 Hom.: 428 Cov.: 32 AF XY: 0.0594 AC XY: 4416 AN XY: 74316

African (AFR) AF: 0.0245 AC: 1015 AN: 41466

American (AMR) AF: 0.0612 AC: 935 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 308 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0266 AC: 128 AN: 4812

European-Finnish (FIN) AF: 0.0464 AC: 490 AN: 10558

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0944 AC: 6415 AN: 67974

Other (OTH) AF: 0.0716 AC: 151 AN: 2108

Alfa AF: 0.0738 Hom.: 417

Bravo AF: 0.0643

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MEF2A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.62
PhyloP100		-3.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34851361; hg19: chr15-100252892; COSMIC: COSV57537893; COSMIC: COSV57537893;