rs7374394

chr3-185228061-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001966.4(EHHADH):c.463+1371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 148,310 control chromosomes in the GnomAD database, including 47,828 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 0.80 (47828 hom., cov: 24)
• Consequence: EHHADH NM_001966.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHHADH	NM_001966.4	c.463+1371G>A		intron_variant		ENST00000231887.8
EHHADH	NM_001166415.2	c.175+1371G>A		intron_variant
EHHADH	XM_047447640.1	c.-192-1203G>A		intron_variant
EHHADH	XM_047447641.1	c.-162+7229G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHHADH	ENST00000231887.8	c.463+1371G>A		intron_variant		1	NM_001966.4	P1
EHHADH	ENST00000456310.5	c.175+1371G>A		intron_variant		2
EHHADH	ENST00000475987.1	n.491-1203G>A		intron_variant, non_coding_transcript_variant		4
EHHADH	ENST00000483104.5	n.173+7229G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.797 AC: 118154 AN: 148246 Hom.: 47825 Cov.: 24

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.856

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.797 AC: 118186 AN: 148310 Hom.: 47828 Cov.: 24 AF XY: 0.792 AC XY: 57160 AN XY: 72198

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.800

Alfa AF: 0.844 Hom.: 86347

Bravo AF: 0.793

Asia WGS AF: 0.632 AC: 2198 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.25

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: rs7374394; hg19: chr3-184945849;