rs13038432

Variant names:

• chr20-54170763-A-G
• rs13038432
• NM_000782.5:c.543+814T>C

Variant summary

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

The NM_000782.5(CYP24A1):​c.543+814T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 152,100 control chromosomes in the GnomAD database, including 314 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 0.055 (314 hom., cov: 32)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.543+814T>C		intron_variant	Intron 3 of 11	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.543+814T>C		intron_variant	Intron 3 of 11	1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8357 AN: 151982 Hom.: 315 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0690

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

GnomAD4 genome AF: 0.0549 AC: 8356 AN: 152100 Hom.: 314 Cov.: 32 AF XY: 0.0542 AC XY: 4028 AN XY: 74334

African (AFR) AF: 0.0148 AC: 615 AN: 41502

American (AMR) AF: 0.0636 AC: 972 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3470

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5162

South Asian (SAS) AF: 0.0576 AC: 277 AN: 4810

European-Finnish (FIN) AF: 0.0696 AC: 736 AN: 10578

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0780 AC: 5305 AN: 67988

Other (OTH) AF: 0.0682 AC: 144 AN: 2110

Alfa AF: 0.0455 Hom.: 60

Bravo AF: 0.0514

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.91
DANN	Benign	0.43
PhyloP100		-0.42
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: rs13038432; hg19: chr20-52787302;