dbSNP rs2216386: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHHADH	NM_001966.4 link	c.178+503C>T		intron_variant	Intron 2 of 6	ENST00000231887.8	NP_001957.2	Q08426-1
EHHADH	NM_001166415.2 link	c.-111+503C>T		intron_variant	Intron 2 of 6		NP_001159887.1	Q08426-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EHHADH	ENST00000231887.8 link	c.178+503C>T	intron_variant	Intron 2 of 6	1	NM_001966.4	ENSP00000231887.3	Q08426-1
EHHADH	ENST00000456310.5 link	c.-111+503C>T	intron_variant	Intron 2 of 6	2		ENSP00000387746.1	Q08426-2
EHHADH	ENST00000475987.1 link	n.205+503C>T	intron_variant	Intron 2 of 5	4
EHHADH	ENST00000440662.1 link	c.*450C>T	downstream_gene_variant		3		ENSP00000396798.1	C9JJE0

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over