rs2585428

chr20-54170358-C-T

Variant summary

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

The NM_000782.5(CYP24A1):c.544-670G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,866 control chromosomes in the GnomAD database, including 15,746 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 0.45 (15746 hom., cov: 31)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.544-670G>A		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.544-670G>A		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.118-670G>A		intron_variant		1
CYP24A1	ENST00000395955.7	c.544-670G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68822 AN: 151748 Hom.: 15723 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.454 AC: 68888 AN: 151866 Hom.: 15746 Cov.: 31 AF XY: 0.449 AC XY: 33311 AN XY: 74236

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.470

Alfa AF: 0.460 Hom.: 21210

Bravo AF: 0.449

Asia WGS AF: 0.399 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.13
Dann	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs2585428; hg19: chr20-52786897;