rs2762929

Positions:

• chr20-54149656-T-C
• chr20-54149656-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017027692.3(CYP24A1):​c.*11-3189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,826 control chromosomes in the GnomAD database, including 20,499 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 0.50 (20499 hom., cov: 31)
• Consequence: CYP24A1 XM_017027692.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

Genes affected

CYP24A1 (HGNC:2602): (cytochrome P450 family 24 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This mitochondrial protein initiates the degradation of 1,25-dihydroxyvitamin D3, the physiologically active form of vitamin D3, by hydroxylation of the side chain. In regulating the level of vitamin D3, this enzyme plays a role in calcium homeostasis and the vitamin D endocrine system. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	XM_017027692.3	c.*11-3189A>G		intron_variant			XP_016883181.1
CYP24A1	XM_047439938.1	c.*11-3189A>G		intron_variant			XP_047295894.1
		n.54149656T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76037 AN: 151704 Hom.: 20474 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.501 AC: 76107 AN: 151826 Hom.: 20499 Cov.: 31 AF XY: 0.506 AC XY: 37525 AN XY: 74144

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.482

Alfa AF: 0.429 Hom.: 11313

Bravo AF: 0.505

Asia WGS AF: 0.668 AC: 2322 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	3.3
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2762929; hg19: chr20-52766195;