Genetic Variant EHHADH:c.178+503C>T (chr3-185247911-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001966.4(EHHADH):c.178+503C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,168 control chromosomes in the GnomAD database, including 35,809 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 0.67 ( 35787 hom., cov: 33)

Exomes 𝑓: 0.81 ( 22 hom. )

Consequence

EHHADH
NM_001966.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

primary Fanconi syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Fanconi renotubular syndrome 3
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

EHHADH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001966.4. 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
	EHHADH	NM_001966.4	MANE Select	c.178+503C>T		intron	N/A	NP_001957.2	Q08426-1
	EHHADH	NM_001166415.2		c.-111+503C>T		intron	N/A	NP_001159887.1	Q08426-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EHHADH	ENST00000231887.8	TSL:1 MANE Select	c.178+503C>T	intron	N/A	ENSP00000231887.3	Q08426-1
EHHADH	ENST00000890155.1		c.178+503C>T	intron	N/A	ENSP00000560214.1
EHHADH	ENST00000890154.1		c.178+503C>T	intron	N/A	ENSP00000560213.1

Frequencies

GnomAD3 genomes

AF:

0.667

AC:

101419

AN:

151986

Hom.:

35792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.912

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.762

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.810

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.792

Gnomad OTH

AF:

0.692

GnomAD4 exome

AF:

0.813

AC:

AN:

Hom.:

Cov.:

AF XY:

0.868

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.839

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.667

AC:

101425

AN:

152104

Hom.:

35787

Cov.:

AF XY:

0.663

AC XY:

49302

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.446

AC:

18474

AN:

41460

American (AMR)

AF:

0.670

AC:

10236

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.762

AC:

2644

AN:

3470

East Asian (EAS)

AF:

0.412

AC:

2134

AN:

5174

South Asian (SAS)

AF:

0.615

AC:

2964

AN:

4816

European-Finnish (FIN)

AF:

0.810

AC:

8573

AN:

10584

Middle Eastern (MID)

AF:

0.755

AC:

222

AN:

294

European-Non Finnish (NFE)

AF:

0.793

AC:

53887

AN:

67996

Other (OTH)

AF:

0.690

AC:

1459

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1579

3159

4738

6318

7897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.712

Hom.:

7823

Bravo

AF:

0.652

Asia WGS

AF:

0.542

AC:

1884

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.8

(source)

DANN

Benign

0.82

PhyloP100

-0.058

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over