chr20-54149656-T-C

Variant names:

• chr20-54149656-T-C
• rs2762929
• ENST00000792273.1:n.155-18782T>C

Variant summary

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

The ENST00000792273.1(ENSG00000286587):​n.155-18782T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,826 control chromosomes in the GnomAD database, including 20,499 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 0.50 (20499 hom., cov: 31)
• Consequence: ENSG00000286587 ENST00000792273.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3	c.*11-3189A>G		intron_variant	Intron 11 of 11		XP_016883181.1
CYP24A1	XM_047439938.1	c.*11-3189A>G		intron_variant	Intron 10 of 10		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286587	ENST00000792273.1	n.155-18782T>C		intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1	n.145-18782T>C		intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1	n.187-14958T>C		intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1	n.125+25739T>C		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76037 AN: 151704 Hom.: 20474 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.501 AC: 76107 AN: 151826 Hom.: 20499 Cov.: 31 AF XY: 0.506 AC XY: 37525 AN XY: 74144

African (AFR) AF: 0.692 AC: 28658 AN: 41398

American (AMR) AF: 0.425 AC: 6485 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3466

East Asian (EAS) AF: 0.693 AC: 3585 AN: 5172

South Asian (SAS) AF: 0.640 AC: 3072 AN: 4798

European-Finnish (FIN) AF: 0.438 AC: 4601 AN: 10510

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.392 AC: 26626 AN: 67908

Other (OTH) AF: 0.482 AC: 1017 AN: 2110

Alfa AF: 0.429 Hom.: 13188

Bravo AF: 0.505

Asia WGS AF: 0.668 AC: 2322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		-0.040

Splicing

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

Other links and lift over

dbSNP: rs2762929; hg19: chr20-52766195;