rs2762942

Positions:

• chr20-54172386-G-A

Variant summary

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

The ENST00000216862.8(CYP24A1):​c.449+523C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 152,308 control chromosomes in the GnomAD database, including 70,377 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 0.96 (70377 hom., cov: 32)
• Consequence: CYP24A1 ENST00000216862.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582

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 = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.449+523C>T		intron_variant		ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.449+523C>T		intron_variant		1	NM_000782.5	ENSP00000216862	P1
CYP24A1	ENST00000395955.7	c.449+523C>T		intron_variant		1		ENSP00000379285

Frequencies

GnomAD3 genomes AF: 0.961 AC: 146248 AN: 152190 Hom.: 70318 Cov.: 32

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.951

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

GnomAD4 genome AF: 0.961 AC: 146366 AN: 152308 Hom.: 70377 Cov.: 32 AF XY: 0.962 AC XY: 71639 AN XY: 74466

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.971

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.962

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.952

Alfa AF: 0.948 Hom.: 11902

Bravo AF: 0.964

Asia WGS AF: 0.987 AC: 3433 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	0.12
DANN	Benign	0.69

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: rs2762942; hg19: chr20-52788925;