rs3787555

chr20-54166152-C-A

Variant summary

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

The NM_000782.5(CYP24A1):c.641-319G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,078 control chromosomes in the GnomAD database, including 4,769 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 0.23 (4769 hom., cov: 32)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.641-319G>T		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.641-319G>T		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.215-319G>T		intron_variant		1
CYP24A1	ENST00000395955.7	c.641-319G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35565 AN: 151960 Hom.: 4753 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.234 AC: 35610 AN: 152078 Hom.: 4769 Cov.: 32 AF XY: 0.234 AC XY: 17423 AN XY: 74342

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.253

Alfa AF: 0.256 Hom.: 6217

Bravo AF: 0.232

Asia WGS AF: 0.440 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.69
Dann	Benign	0.44

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: rs3787555; hg19: chr20-52782691;