rs3732933

chr3-185193363-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001966.4(EHHADH):c.1035A>G(p.Glu345=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 1,614,088 control chromosomes in the GnomAD database, including 5,761 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.069 (447 hom., cov: 32)
  • Exomes 𝑓: 0.083 (5314 hom.)
• Consequence: EHHADH NM_001966.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

EHHADH (HGNC:3247): (enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase) The protein encoded by this gene is a bifunctional enzyme and is one of the four enzymes of the peroxisomal beta-oxidation pathway. The N-terminal region of the encoded protein contains enoyl-CoA hydratase activity while the C-terminal region contains 3-hydroxyacyl-CoA dehydrogenase activity. Defects in this gene are a cause of peroxisomal disorders such as Zellweger syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHHADH	NM_001966.4	c.1035A>G	p.Glu345=	synonymous_variant	7/7	ENST00000231887.8
EHHADH	NM_001166415.2	c.747A>G	p.Glu249=	synonymous_variant	7/7
EHHADH	XM_047447640.1	c.411A>G	p.Glu137=	synonymous_variant	5/5
EHHADH	XM_047447641.1	c.411A>G	p.Glu137=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHHADH	ENST00000231887.8	c.1035A>G	p.Glu345=	synonymous_variant	7/7	1	NM_001966.4	P1
EHHADH	ENST00000456310.5	c.747A>G	p.Glu249=	synonymous_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10487 AN: 152200 Hom.: 448 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.0632

GnomAD3 exomes AF: 0.0831 AC: 20864 AN: 250966 Hom.: 1007 AF XY: 0.0857 AC XY: 11620 AN XY: 135664

Gnomad AFR exome AF: 0.0351

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.0643

Gnomad EAS exome AF: 0.0718

Gnomad SAS exome AF: 0.126

Gnomad FIN exome AF: 0.0576

Gnomad NFE exome AF: 0.0792

Gnomad OTH exome AF: 0.0768

GnomAD4 exome AF: 0.0832 AC: 121633 AN: 1461770 Hom.: 5314 Cov.: 32 AF XY: 0.0847 AC XY: 61567 AN XY: 727176

Gnomad4 AFR exome AF: 0.0327

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0670

Gnomad4 EAS exome AF: 0.0779

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0563

Gnomad4 NFE exome AF: 0.0826

Gnomad4 OTH exome AF: 0.0794

GnomAD4 genome AF: 0.0689 AC: 10491 AN: 152318 Hom.: 447 Cov.: 32 AF XY: 0.0702 AC XY: 5227 AN XY: 74464

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.0888

Gnomad4 ASJ AF: 0.0688

Gnomad4 EAS AF: 0.0702

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0831

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0790 Hom.: 858

Bravo AF: 0.0686

Asia WGS AF: 0.0920 AC: 319 AN: 3478

EpiCase AF: 0.0802

EpiControl AF: 0.0808

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	6.0
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs3732933; hg19: chr3-184911151; COSMIC: COSV51633315; COSMIC: COSV51633315;