3-185222710-C-T

Variant names:

• chr3-185222710-C-T
• rs6779662
• NM_001966.4:c.464-4470G>A

Variant summary

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

The NM_001966.4(EHHADH):​c.464-4470G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,256 control chromosomes in the GnomAD database, including 61,968 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 0.90 (61968 hom., cov: 32)
• Consequence: EHHADH NM_001966.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34
• Publications: 3 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHHADH	NM_001966.4	MANE Select	c.464-4470G>A		intron	N/A	NP_001957.2	Q08426-1
	EHHADH	NM_001166415.2		c.176-4470G>A		intron	N/A	NP_001159887.1	Q08426-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHHADH	ENST00000231887.8	TSL:1 MANE Select	c.464-4470G>A		intron	N/A	ENSP00000231887.3	Q08426-1
	EHHADH	ENST00000890155.1		c.464-4470G>A		intron	N/A	ENSP00000560214.1
	EHHADH	ENST00000890154.1		c.463+6722G>A		intron	N/A	ENSP00000560213.1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 137079 AN: 152138 Hom.: 61926 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.892

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

GnomAD4 genome AF: 0.901 AC: 137178 AN: 152256 Hom.: 61968 Cov.: 32 AF XY: 0.898 AC XY: 66844 AN XY: 74434

African (AFR) AF: 0.894 AC: 37147 AN: 41534

American (AMR) AF: 0.875 AC: 13389 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3113 AN: 3472

East Asian (EAS) AF: 0.699 AC: 3611 AN: 5164

South Asian (SAS) AF: 0.823 AC: 3970 AN: 4824

European-Finnish (FIN) AF: 0.936 AC: 9931 AN: 10610

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.926 AC: 62973 AN: 68034

Other (OTH) AF: 0.889 AC: 1878 AN: 2112

Alfa AF: 0.916 Hom.: 72374

Bravo AF: 0.898

Asia WGS AF: 0.787 AC: 2737 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.54
DANN	Benign	0.73
PhyloP100		-3.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6779662;

hg19: chr3-184940498;