20-54166152-C-A

Variant names:

• chr20-54166152-C-A
• rs3787555
• NM_000782.5:c.641-319G>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.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
• Publications: 19 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 = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.641-319G>T		intron_variant	Intron 4 of 11	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.641-319G>T		intron_variant	Intron 4 of 11	1	NM_000782.5	ENSP00000216862.3

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

African (AFR) AF: 0.151 AC: 6269 AN: 41490

American (AMR) AF: 0.212 AC: 3248 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1007 AN: 3470

East Asian (EAS) AF: 0.616 AC: 3179 AN: 5164

South Asian (SAS) AF: 0.339 AC: 1632 AN: 4814

European-Finnish (FIN) AF: 0.186 AC: 1970 AN: 10584

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17407 AN: 67954

Other (OTH) AF: 0.253 AC: 533 AN: 2110

Alfa AF: 0.250 Hom.: 7455

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
PhyloP100		-0.72
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: rs3787555; hg19: chr20-52782691;