10-89206789-C-T

Position:

• chr10-89206789-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_003956.4(CH25H):​c.504G>A​(p.Ala168=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CH25H	NM_003956.4	c.504G>A	p.Ala168=	synonymous_variant	1/1	ENST00000371852.4	NP_003947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CH25H	ENST00000371852.4	c.504G>A	p.Ala168=	synonymous_variant	1/1		NM_003956.4	ENSP00000360918	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21231 AN: 152110 Hom.: 3030 Cov.: 33

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

GnomAD3 exomes AF: 0.221 AC: 55525 AN: 251432 Hom.: 10207 AF XY: 0.217 AC XY: 29542 AN XY: 135896

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 SAS exome AF: 0.293

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.: 35 AF XY: 0.153 AC XY: 110992 AN XY: 727230

Gnomad4 AFR exome AF: 0.0211

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.762

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.140 AC: 21263 AN: 152228 Hom.: 3041 Cov.: 33 AF XY: 0.152 AC XY: 11305 AN XY: 74404

Gnomad4 AFR AF: 0.0254

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.140

Alfa AF: 0.0965 Hom.: 527

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
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs4078488; hg19: chr10-90966546; COSMIC: COSV64092342;