rs16859825

Variant names:

• chr3-185213225-T-C
• rs16859825
• NM_001966.4:c.568+4911A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001966.4(EHHADH):​c.568+4911A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,418 control chromosomes in the GnomAD database, including 1,732 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 0.13 (1732 hom., cov: 30)
• Consequence: EHHADH NM_001966.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• Publications: 6 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 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.568+4911A>G		intron	N/A	NP_001957.2	Q08426-1
	EHHADH	NM_001166415.2		c.280+4911A>G		intron	N/A	NP_001159887.1	Q08426-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHHADH	ENST00000231887.8	TSL:1 MANE Select	c.568+4911A>G		intron	N/A	ENSP00000231887.3	Q08426-1
	EHHADH	ENST00000890155.1		c.568+4911A>G		intron	N/A	ENSP00000560214.1
	EHHADH	ENST00000890154.1		c.464-8468A>G		intron	N/A	ENSP00000560213.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19005 AN: 151302 Hom.: 1719 Cov.: 30

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0727

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19057 AN: 151418 Hom.: 1732 Cov.: 30 AF XY: 0.125 AC XY: 9245 AN XY: 73996

African (AFR) AF: 0.250 AC: 10296 AN: 41222

American (AMR) AF: 0.119 AC: 1806 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3470

East Asian (EAS) AF: 0.0660 AC: 339 AN: 5136

South Asian (SAS) AF: 0.0728 AC: 348 AN: 4778

European-Finnish (FIN) AF: 0.0521 AC: 542 AN: 10404

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0772 AC: 5238 AN: 67864

Other (OTH) AF: 0.104 AC: 220 AN: 2110

Alfa AF: 0.0907 Hom.: 3102

Bravo AF: 0.135

Asia WGS AF: 0.0870 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16859825; hg19: chr3-184931013;