Genetic Variant EPHX3:c.*463G>A (chr19-15226974-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024794.3(EPHX3):c.*463G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 163,946 control chromosomes in the GnomAD database, including 50,676 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 0.78 ( 47582 hom., cov: 32)

Exomes 𝑓: 0.71 ( 3094 hom. )

Consequence

EPHX3
NM_024794.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0550

Publications

5 publications found

Variant links:

Genes affected

EPHX3 (HGNC:23760): (epoxide hydrolase 3) Enables epoxide hydrolase activity. Involved in epoxide metabolic process. Located in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]

EPHX3 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EPHX3	NM_024794.3 link	c.*463G>A	3_prime_UTR_variant	Exon 7 of 7	ENST00000221730.8	NP_079070.1	Q9H6B9A0A024R7F3
EPHX3	NM_001142886.2 link	c.*463G>A	3_prime_UTR_variant	Exon 8 of 8		NP_001136358.1	Q9H6B9A0A024R7F3
EPHX3	XM_024451725.2 link	c.*463G>A	3_prime_UTR_variant	Exon 9 of 9		XP_024307493.1
EPHX3	XM_047439452.1 link	c.*463G>A	3_prime_UTR_variant	Exon 9 of 9		XP_047295408.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPHX3	ENST00000221730.8 link	c.*463G>A	3_prime_UTR_variant	Exon 7 of 7	1	NM_024794.3	ENSP00000221730.2	Q9H6B9
EPHX3	ENST00000435261.5 link	c.*463G>A	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000410323.1	Q9H6B9
EPHX3	ENST00000602233.5 link	c.*463G>A	3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000469345.1	Q9H6B9

Frequencies

GnomAD3 genomes

AF:

0.783

AC:

118963

AN:

151998

Hom.:

47528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.945

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.798

Gnomad ASJ

AF:

0.765

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.760

Gnomad FIN

AF:

0.639

Gnomad MID

AF:

0.860

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.807

GnomAD4 exome

AF:

0.712

AC:

8424

AN:

11830

Hom.:

3094

Cov.:

AF XY:

0.717

AC XY:

4262

AN XY:

5944

show subpopulations

African (AFR)

AF:

0.975

AC:

238

AN:

244

American (AMR)

AF:

0.768

AC:

1398

AN:

1820

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

195

AN:

258

East Asian (EAS)

AF:

0.791

AC:

367

AN:

464

South Asian (SAS)

AF:

0.725

AC:

650

AN:

896

European-Finnish (FIN)

AF:

0.538

AC:

143

AN:

266

Middle Eastern (MID)

AF:

0.912

AC:

AN:

European-Non Finnish (NFE)

AF:

0.685

AC:

4974

AN:

7264

Other (OTH)

AF:

0.733

AC:

428

AN:

584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

109

219

328

438

547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.783

AC:

119075

AN:

152116

Hom.:

47582

Cov.:

AF XY:

0.781

AC XY:

58048

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.945

AC:

39239

AN:

41524

American (AMR)

AF:

0.797

AC:

12184

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

2653

AN:

3470

East Asian (EAS)

AF:

0.813

AC:

4206

AN:

5176

South Asian (SAS)

AF:

0.759

AC:

3666

AN:

4828

European-Finnish (FIN)

AF:

0.639

AC:

6746

AN:

10552

Middle Eastern (MID)

AF:

0.873

AC:

255

AN:

292

European-Non Finnish (NFE)

AF:

0.703

AC:

47776

AN:

67974

Other (OTH)

AF:

0.806

AC:

1703

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1237

2474

3710

4947

6184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.743

Hom.:

28307

Bravo

AF:

0.803

Asia WGS

AF:

0.796

AC:

2767

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.77

(source)

DANN

Benign

0.38

PhyloP100

-0.055

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr19-15226974-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over