rs2762942

Variant names:

• chr20-54172386-G-A
• rs2762942
• NM_000782.5:c.449+523C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000782.5(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 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 7 publications found

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]

CYP24A1 Gene-Disease associations (from GenCC):

• hypercalcemia, infantile, 1

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• autosomal recessive infantile hypercalcemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	NM_000782.5	MANE Select	c.449+523C>T		intron	N/A	NP_000773.2
	CYP24A1	NM_001424340.1		c.449+523C>T		intron	N/A	NP_001411269.1
	CYP24A1	NM_001424341.1		c.449+523C>T		intron	N/A	NP_001411270.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.449+523C>T		intron	N/A	ENSP00000216862.3
	CYP24A1	ENST00000395955.7	TSL:1	c.449+523C>T		intron	N/A	ENSP00000379285.3
	CYP24A1	ENST00000869535.1		c.449+523C>T		intron	N/A	ENSP00000539594.1

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

African (AFR) AF: 0.990 AC: 41167 AN: 41572

American (AMR) AF: 0.965 AC: 14763 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3368 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5187 AN: 5188

South Asian (SAS) AF: 0.962 AC: 4646 AN: 4830

European-Finnish (FIN) AF: 0.953 AC: 10110 AN: 10604

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64025 AN: 68036

Other (OTH) AF: 0.952 AC: 2004 AN: 2106

Alfa AF: 0.960 Hom.: 30534

Bravo AF: 0.964

Asia WGS AF: 0.987 AC: 3433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.69
PhyloP100		-0.58
PromoterAI		0.0032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2762942; hg19: chr20-52788925;