20-54166319-C-T

Variant names:

• chr20-54166319-C-T
• rs2244719
• NM_000782.5:c.641-486G>A

Variant summary

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

The NM_000782.5(CYP24A1):​c.641-486G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,988 control chromosomes in the GnomAD database, including 28,686 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 0.60 (28686 hom., cov: 31)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 24 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 = 0.837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000782.5. 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
	CYP24A1	NM_000782.5	MANE Select	c.641-486G>A		intron	N/A	NP_000773.2
	CYP24A1	NM_001424340.1		c.641-486G>A		intron	N/A	NP_001411269.1
	CYP24A1	NM_001424341.1		c.641-486G>A		intron	N/A	NP_001411270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.641-486G>A		intron	N/A	ENSP00000216862.3
	CYP24A1	ENST00000395955.7	TSL:1	c.641-486G>A		intron	N/A	ENSP00000379285.3
	CYP24A1	ENST00000395954.3	TSL:1	c.215-486G>A		intron	N/A	ENSP00000379284.3

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91806 AN: 151870 Hom.: 28647 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.605 AC: 91901 AN: 151988 Hom.: 28686 Cov.: 31 AF XY: 0.606 AC XY: 45002 AN XY: 74254

African (AFR) AF: 0.747 AC: 30957 AN: 41458

American (AMR) AF: 0.481 AC: 7354 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2066 AN: 3472

East Asian (EAS) AF: 0.858 AC: 4439 AN: 5172

South Asian (SAS) AF: 0.686 AC: 3301 AN: 4810

European-Finnish (FIN) AF: 0.553 AC: 5831 AN: 10544

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36056 AN: 67940

Other (OTH) AF: 0.593 AC: 1251 AN: 2108

Alfa AF: 0.555 Hom.: 6652

Bravo AF: 0.602

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.062
DANN	Benign	0.51
PhyloP100		-0.95
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: rs2244719; hg19: chr20-52782858;