Variant 3-185193363-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001966.4(EHHADH):c.1035A>G(p.Glu345Glu) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Variant links:

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]

EHHADH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
EHHADH	NM_001966.4 linkuse as main transcript	c.1035A>G	p.Glu345Glu	synonymous_variant	7/7	ENST00000231887.8	NP_001957.2	Q08426-1
EHHADH	NM_001166415.2 linkuse as main transcript	c.747A>G	p.Glu249Glu	synonymous_variant	7/7		NP_001159887.1	Q08426-2
EHHADH	XM_047447640.1 linkuse as main transcript	c.411A>G	p.Glu137Glu	synonymous_variant	5/5		XP_047303596.1
EHHADH	XM_047447641.1 linkuse as main transcript	c.411A>G	p.Glu137Glu	synonymous_variant	4/4		XP_047303597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHHADH	ENST00000231887.8 linkuse as main transcript	c.1035A>G	p.Glu345Glu	synonymous_variant	7/7	1	NM_001966.4	ENSP00000231887.3		Q08426-1
EHHADH	ENST00000456310.5 linkuse as main transcript	c.747A>G	p.Glu249Glu	synonymous_variant	7/7	2		ENSP00000387746.1		Q08426-2

Frequencies

GnomAD3 genomes

AF:

0.0689

AC:

10487

AN:

152200

Hom.:

448

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0847

AC XY:

61567

AN XY:

727176

show subpopulations

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.:

AF XY:

0.0702

AC XY:

5227

AN XY:

74464

show subpopulations

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over