rs11699278

Variant names:

• chr20-54172253-G-A
• rs11699278
• NM_000782.5:c.450-583C>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.450-583C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 152,152 control chromosomes in the GnomAD database, including 206 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 0.042 (206 hom., cov: 32)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.058 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.450-583C>T		intron	N/A	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.450-583C>T		intron	N/A	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.450-583C>T		intron	N/A	NP_001411270.1	Q07973-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.450-583C>T		intron	N/A	ENSP00000216862.3	Q07973-1
	CYP24A1	ENST00000395955.7	TSL:1	c.450-583C>T		intron	N/A	ENSP00000379285.3	Q07973-2
	CYP24A1	ENST00000869535.1		c.450-583C>T		intron	N/A	ENSP00000539594.1

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6333 AN: 152034 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00686

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0416 AC: 6330 AN: 152152 Hom.: 206 Cov.: 32 AF XY: 0.0436 AC XY: 3240 AN XY: 74372

African (AFR) AF: 0.00997 AC: 414 AN: 41516

American (AMR) AF: 0.0241 AC: 368 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00665 AC: 32 AN: 4810

European-Finnish (FIN) AF: 0.121 AC: 1282 AN: 10554

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0595 AC: 4049 AN: 68008

Other (OTH) AF: 0.0284 AC: 60 AN: 2114

Alfa AF: 0.0559 Hom.: 360

Bravo AF: 0.0329

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.82
PhyloP100		0.066
PromoterAI		-0.014	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: rs11699278; hg19: chr20-52788792;