3-185192348-T-C

Position:

chr3-185192348-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001966.4(EHHADH):c.2050A>G(p.Arg684Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000868 in 1,614,170 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 7 hom. )

Consequence

EHHADH
NM_001966.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.826

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004082173).

BP6

Variant 3-185192348-T-C is Benign according to our data. Variant chr3-185192348-T-C is described in ClinVar as [Benign]. Clinvar id is 712443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00466 (709/152294) while in subpopulation AFR AF= 0.0164 (681/41566). AF 95% confidence interval is 0.0154. There are 10 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 709 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EHHADH	NM_001966.4 linkuse as main transcript	c.2050A>G	p.Arg684Gly	missense_variant	7/7	ENST00000231887.8
EHHADH	NM_001166415.2 linkuse as main transcript	c.1762A>G	p.Arg588Gly	missense_variant	7/7
EHHADH	XM_047447640.1 linkuse as main transcript	c.1426A>G	p.Arg476Gly	missense_variant	5/5
EHHADH	XM_047447641.1 linkuse as main transcript	c.1426A>G	p.Arg476Gly	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHHADH	ENST00000231887.8 linkuse as main transcript	c.2050A>G	p.Arg684Gly	missense_variant	7/7	1	NM_001966.4	P1	Q08426-1
EHHADH	ENST00000456310.5 linkuse as main transcript	c.1762A>G	p.Arg588Gly	missense_variant	7/7	2			Q08426-2

Frequencies

GnomAD3 genomes

AF:

0.00465

AC:

707

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00125

AC:

313

AN:

251136

Hom.:

AF XY:

0.00100

AC XY:

136

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000473

AC:

692

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

279

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0170

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000977

GnomAD4 genome

AF:

0.00466

AC:

709

AN:

152294

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

346

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0164

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000842

Hom.:

Bravo

AF:

0.00547

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00147

AC:

179

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.86

L;.

MutationTaster

Benign

0.59

D;D

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.022

D;T

Sift4G

Benign

0.30

T;T

Polyphen

0.20

B;.

Vest4

0.20

MVP

0.61

MPC

0.13

ClinPred

0.0051

GERP RS

1.7

Varity_R

0.15

gMVP

0.40

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