rs6805633

Variant names:

• chr3-185196064-T-A
• rs6805633
• NM_001966.4:c.911-2577A>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.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
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 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.911-2577A>T		intron	N/A	NP_001957.2
	EHHADH	NM_001166415.2		c.623-2577A>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.911-2577A>T		intron	N/A	ENSP00000231887.3
	EHHADH	ENST00000456310.5	TSL:2	c.623-2577A>T		intron	N/A	ENSP00000387746.1

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

African (AFR) AF: 0.0630 AC: 2620 AN: 41572

American (AMR) AF: 0.0469 AC: 717 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.156 AC: 809 AN: 5180

South Asian (SAS) AF: 0.0648 AC: 313 AN: 4832

European-Finnish (FIN) AF: 0.0408 AC: 433 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0185 AC: 1259 AN: 68028

Other (OTH) AF: 0.0279 AC: 59 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.51
PhyloP100		0.31
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: rs6805633; hg19: chr3-184913852;