rs16859825

Positions:

• chr3-185213225-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHHADH	NM_001966.4	c.568+4911A>G		intron_variant		ENST00000231887.8	NP_001957.2
EHHADH	NM_001166415.2	c.280+4911A>G		intron_variant			NP_001159887.1
EHHADH	XM_047447640.1	c.-57+4911A>G		intron_variant			XP_047303596.1
EHHADH	XM_047447641.1	c.-57+4911A>G		intron_variant			XP_047303597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHHADH	ENST00000231887.8	c.568+4911A>G		intron_variant		1	NM_001966.4	ENSP00000231887	P1
EHHADH	ENST00000456310.5	c.280+4911A>G		intron_variant		2		ENSP00000387746
EHHADH	ENST00000483104.5	n.174-8468A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.0660

Gnomad4 SAS AF: 0.0728

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0772

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0813 Hom.: 994

Bravo AF: 0.135

Asia WGS AF: 0.0870 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs16859825; hg19: chr3-184931013;