rs2216386

chr3-185247911-G-Achr3-185247911-G-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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=-0.88).
• 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/exons	MANE	UniProt
EHHADH	NM_001966.4	c.178+503C>T		intron_variant		ENST00000231887.8
EHHADH	NM_001166415.2	c.-111+503C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHHADH	ENST00000231887.8	c.178+503C>T		intron_variant		1	NM_001966.4	P1
EHHADH	ENST00000456310.5	c.-111+503C>T		intron_variant		2
EHHADH	ENST00000475987.1	n.205+503C>T		intron_variant, non_coding_transcript_variant		4
EHHADH	ENST00000440662.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101419 AN: 151986 Hom.: 35792 Cov.: 33

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: 52 AN: 64 Hom.: 22 Cov.: 0 AF XY: 0.868 AC XY: 33 AN XY: 38

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.667 AC: 101425 AN: 152104 Hom.: 35787 Cov.: 33 AF XY: 0.663 AC XY: 49302 AN XY: 74360

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.690

Alfa AF: 0.719 Hom.: 7750

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
Dann	Benign	0.82

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: rs2216386; hg19: chr3-184965699;