chr20-54153364-T-A

Variant names:

• chr20-54153364-T-A
• rs2762933
• ENST00000792273.1:n.155-15074T>A

Variant summary

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

The ENST00000792273.1(ENSG00000286587):​n.155-15074T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,200 control chromosomes in the GnomAD database, including 5,775 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 0.26 (5775 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000286587 ENST00000792273.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 8 publications found

Genes affected

ENSG00000286587 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.*1408A>T		downstream_gene_variant		ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.*1408A>T		downstream_gene_variant		1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39953 AN: 152082 Hom.: 5769 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.263 AC: 39997 AN: 152200 Hom.: 5775 Cov.: 33 AF XY: 0.267 AC XY: 19865 AN XY: 74422

African (AFR) AF: 0.165 AC: 6859 AN: 41546

American (AMR) AF: 0.223 AC: 3417 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3468

East Asian (EAS) AF: 0.102 AC: 531 AN: 5184

South Asian (SAS) AF: 0.330 AC: 1590 AN: 4822

European-Finnish (FIN) AF: 0.384 AC: 4063 AN: 10576

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21514 AN: 67990

Other (OTH) AF: 0.268 AC: 565 AN: 2110

Alfa AF: 0.296 Hom.: 843

Bravo AF: 0.242

Asia WGS AF: 0.237 AC: 823 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.43
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs2762933; hg19: chr20-52769903;