20-54145879-G-T

Variant names:

• chr20-54145879-G-T
• rs2762926
• XM_017027692.3:c.*599C>A

Variant summary

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

The XM_017027692.3(CYP24A1):​c.*599C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,054 control chromosomes in the GnomAD database, including 26,537 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 0.57 (26537 hom., cov: 33)
• Consequence: CYP24A1 XM_017027692.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3	c.*599C>A		3_prime_UTR_variant	Exon 12 of 12		XP_016883181.1
CYP24A1	XM_047439938.1	c.*599C>A		3_prime_UTR_variant	Exon 11 of 11		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286587	ENST00000792273.1	n.155-22559G>T		intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1	n.145-22559G>T		intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1	n.187-18735G>T		intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1	n.125+21962G>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86372 AN: 151936 Hom.: 26499 Cov.: 33

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.569 AC: 86462 AN: 152054 Hom.: 26537 Cov.: 33 AF XY: 0.573 AC XY: 42595 AN XY: 74300

African (AFR) AF: 0.787 AC: 32677 AN: 41510

American (AMR) AF: 0.469 AC: 7165 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1958 AN: 3464

East Asian (EAS) AF: 0.833 AC: 4320 AN: 5184

South Asian (SAS) AF: 0.737 AC: 3554 AN: 4824

European-Finnish (FIN) AF: 0.469 AC: 4934 AN: 10512

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30243 AN: 67970

Other (OTH) AF: 0.552 AC: 1164 AN: 2110

Alfa AF: 0.483 Hom.: 74277

Bravo AF: 0.573

Asia WGS AF: 0.784 AC: 2725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.27
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs2762926; hg19: chr20-52762418;