rs6805633

Positions:

• chr3-185196064-T-A

Variant summary

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

The NM_001966.4(EHHADH):​c.911-2577A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 152,314 control chromosomes in the GnomAD database, including 200 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 0.041 (200 hom., cov: 32)
• Consequence: EHHADH NM_001966.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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 (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHHADH	NM_001966.4	c.911-2577A>T		intron_variant		ENST00000231887.8	NP_001957.2
EHHADH	NM_001166415.2	c.623-2577A>T		intron_variant			NP_001159887.1
EHHADH	XM_047447640.1	c.287-2577A>T		intron_variant			XP_047303596.1
EHHADH	XM_047447641.1	c.287-2577A>T		intron_variant			XP_047303597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHHADH	ENST00000231887.8	c.911-2577A>T		intron_variant		1	NM_001966.4	ENSP00000231887	P1
EHHADH	ENST00000456310.5	c.623-2577A>T		intron_variant		2		ENSP00000387746

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6226 AN: 152196 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0409 AC: 6234 AN: 152314 Hom.: 200 Cov.: 32 AF XY: 0.0437 AC XY: 3254 AN XY: 74472

Gnomad4 AFR AF: 0.0630

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0339 Hom.: 17

Bravo AF: 0.0409

Asia WGS AF: 0.0890 AC: 310 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	0.82
DANN	Benign	0.51

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: rs6805633; hg19: chr3-184913852;