chr20-54146792-T-C

Position:

• chr20-54146792-T-C

Variant summary

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

The XM_017027692.3(CYP24A1):​c.*11-325A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,020 control chromosomes in the GnomAD database, including 3,442 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 0.20 (3442 hom., cov: 32)
• Consequence: CYP24A1 XM_017027692.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	XM_017027692.3	c.*11-325A>G		intron_variant			XP_016883181.1
CYP24A1	XM_047439938.1	c.*11-325A>G		intron_variant			XP_047295894.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29889 AN: 151902 Hom.: 3440 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.197 AC: 29907 AN: 152020 Hom.: 3442 Cov.: 32 AF XY: 0.197 AC XY: 14637 AN XY: 74298

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.170

Alfa AF: 0.144 Hom.: 2216

Bravo AF: 0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.017
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6097797; hg19: chr20-52763331;