Variant 3-185192281-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001966.4(EHHADH):c.2117A>T(p.Asn706Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,613,598 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 23 hom. )

Consequence

EHHADH
NM_001966.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.34

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0153059065).

BP6

Variant 3-185192281-T-A is Benign according to our data. Variant chr3-185192281-T-A is described in ClinVar as [Benign]. Clinvar id is 501352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-185192281-T-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 646 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EHHADH	NM_001966.4 linkuse as main transcript	c.2117A>T	p.Asn706Ile	missense_variant	7/7	ENST00000231887.8
EHHADH	NM_001166415.2 linkuse as main transcript	c.1829A>T	p.Asn610Ile	missense_variant	7/7
EHHADH	XM_047447640.1 linkuse as main transcript	c.1493A>T	p.Asn498Ile	missense_variant	5/5
EHHADH	XM_047447641.1 linkuse as main transcript	c.1493A>T	p.Asn498Ile	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHHADH	ENST00000231887.8 linkuse as main transcript	c.2117A>T	p.Asn706Ile	missense_variant	7/7	1	NM_001966.4	P1	Q08426-1
EHHADH	ENST00000456310.5 linkuse as main transcript	c.1829A>T	p.Asn610Ile	missense_variant	7/7	2			Q08426-2

Frequencies

GnomAD3 genomes

AF:

0.00425

AC:

645

AN:

151648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00251

Gnomad FIN

AF:

0.00114

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00506

Gnomad OTH

AF:

0.00769

GnomAD3 exomes

AF:

0.00443

AC:

1112

AN:

251024

Hom.:

AF XY:

0.00472

AC XY:

640

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00744

Gnomad ASJ exome

AF:

0.00725

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00317

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00537

Gnomad OTH exome

AF:

0.00474

GnomAD4 exome

AF:

0.00453

AC:

6624

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

3288

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00747

Gnomad4 ASJ exome

AF:

0.00742

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00328

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.00484

Gnomad4 OTH exome

AF:

0.00493

GnomAD4 genome

AF:

0.00426

AC:

646

AN:

151766

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

310

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00251

Gnomad4 FIN

AF:

0.00114

Gnomad4 NFE

AF:

0.00507

Gnomad4 OTH

AF:

0.00761

Alfa

AF:

0.00218

Hom.:

Bravo

AF:

0.00490

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00418

AC:

507

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00616

EpiControl

AF:

0.00753

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	EHHADH: BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 10, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.015

T;T

MetaSVM

Uncertain

0.018

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.56

N;N

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.97

D;.

Vest4

0.44

MVP

0.81

MPC

0.40

ClinPred

0.012

GERP RS

4.8

Varity_R

0.53

gMVP

0.56

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