Genetic Variant CH25H:p.Ala168Ala (chr10-89206789-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_003956.4(CH25H):c.504G>A(p.Ala168Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,614,092 control chromosomes in the GnomAD database, including 30,213 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 0.14 ( 3041 hom., cov: 33)

Exomes 𝑓: 0.15 ( 27172 hom. )

Consequence

CH25H
NM_003956.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

14 publications found

Variant links:

Genes affected

CH25H (HGNC:1907): (cholesterol 25-hydroxylase) This is an intronless gene that is involved in cholesterol and lipid metabolism. The encoded protein is a membrane protein and contains clusters of histidine residues essential for catalytic activity. Unlike most other sterol hydroxylases, this enzyme is a member of a small family of enzymes that utilize diiron cofactors to catalyze the hydroxylation of hydrophobic substrates. [provided by RefSeq, Jul 2008]

CH25H links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CH25H	NM_003956.4 link	c.504G>A	p.Ala168Ala	synonymous_variant	Exon 1 of 1	ENST00000371852.4	NP_003947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CH25H	ENST00000371852.4 link	c.504G>A	p.Ala168Ala	synonymous_variant	Exon 1 of 1	6	NM_003956.4	ENSP00000360918.2

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21231

AN:

152110

Hom.:

3030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.754

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.138

GnomAD2 exomes

AF:

0.221

AC:

55525

AN:

251432

AF XY:

0.217

show subpopulations

Gnomad AFR exome

AF:

0.0222

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.761

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.148

AC:

216797

AN:

1461864

Hom.:

27172

Cov.:

AF XY:

0.153

AC XY:

110992

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0211

AC:

707

AN:

33480

American (AMR)

AF:

0.303

AC:

13565

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

4160

AN:

26136

East Asian (EAS)

AF:

0.762

AC:

30239

AN:

39700

South Asian (SAS)

AF:

0.289

AC:

24970

AN:

86256

European-Finnish (FIN)

AF:

0.241

AC:

12896

AN:

53420

Middle Eastern (MID)

AF:

0.150

AC:

866

AN:

5768

European-Non Finnish (NFE)

AF:

0.107

AC:

119257

AN:

1111986

Other (OTH)

AF:

0.168

AC:

10137

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

11650

23300

34949

46599

58249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4706

9412

14118

18824

23530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.140

AC:

21263

AN:

152228

Hom.:

3041

Cov.:

AF XY:

0.152

AC XY:

11305

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0254

AC:

1054

AN:

41560

American (AMR)

AF:

0.217

AC:

3318

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

578

AN:

3470

East Asian (EAS)

AF:

0.754

AC:

3896

AN:

5166

South Asian (SAS)

AF:

0.320

AC:

1543

AN:

4828

European-Finnish (FIN)

AF:

0.251

AC:

2650

AN:

10574

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7780

AN:

68022

Other (OTH)

AF:

0.140

AC:

295

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

823

1645

2468

3290

4113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

1375

Bravo

AF:

0.134

Asia WGS

AF:

0.454

AC:

1575

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

9.6

(source)

DANN

Benign

0.84

PhyloP100

-1.1

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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