XM_017027692.3:c.*537C>T

Variant names:

• chr20-54145941-G-A
• rs2585413
• XM_017027692.3:c.*537C>T

Variant summary

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

The XM_017027692.3(CYP24A1):​c.*537C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,124 control chromosomes in the GnomAD database, including 8,746 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 0.34 (8746 hom., cov: 33)
• Consequence: CYP24A1 XM_017027692.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000792273.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286587	ENST00000792273.1		n.155-22497G>A		intron	N/A
	ENSG00000286587	ENST00000792274.1		n.145-22497G>A		intron	N/A
	ENSG00000286587	ENST00000792275.1		n.187-18673G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51147 AN: 152006 Hom.: 8743 Cov.: 33

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.336 AC: 51178 AN: 152124 Hom.: 8746 Cov.: 33 AF XY: 0.343 AC XY: 25519 AN XY: 74376

African (AFR) AF: 0.395 AC: 16377 AN: 41490

American (AMR) AF: 0.324 AC: 4956 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2068 AN: 5170

South Asian (SAS) AF: 0.425 AC: 2051 AN: 4830

European-Finnish (FIN) AF: 0.343 AC: 3622 AN: 10550

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19877 AN: 68012

Other (OTH) AF: 0.321 AC: 678 AN: 2110

Alfa AF: 0.309 Hom.: 3857

Bravo AF: 0.335

Asia WGS AF: 0.412 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		0.040

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2585413; hg19: chr20-52762480;