NM_001966.4:c.569-3401A>T

Variant names:

• chr3-185208158-T-A
• rs2160815
• NM_001966.4:c.569-3401A>T

Variant summary

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

The NM_001966.4(EHHADH):​c.569-3401A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,262 control chromosomes in the GnomAD database, including 1,531 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 (1531 hom., cov: 33)
• Consequence: EHHADH NM_001966.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHHADH	NM_001966.4	MANE Select	c.569-3401A>T		intron	N/A	NP_001957.2
	EHHADH	NM_001166415.2		c.281-3401A>T		intron	N/A	NP_001159887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHHADH	ENST00000231887.8	TSL:1 MANE Select	c.569-3401A>T		intron	N/A	ENSP00000231887.3
	EHHADH	ENST00000456310.5	TSL:2	c.281-3401A>T		intron	N/A	ENSP00000387746.1
	EHHADH	ENST00000483104.5	TSL:5	n.174-3401A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20428 AN: 152144 Hom.: 1532 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.134 AC: 20418 AN: 152262 Hom.: 1531 Cov.: 33 AF XY: 0.138 AC XY: 10260 AN XY: 74426

African (AFR) AF: 0.108 AC: 4472 AN: 41564

American (AMR) AF: 0.168 AC: 2577 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1531 AN: 5176

South Asian (SAS) AF: 0.175 AC: 846 AN: 4824

European-Finnish (FIN) AF: 0.184 AC: 1951 AN: 10590

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8128 AN: 68022

Other (OTH) AF: 0.137 AC: 289 AN: 2116

Alfa AF: 0.132 Hom.: 189

Bravo AF: 0.137

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.95
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: rs2160815; hg19: chr3-184925946;