NM_000782.5:c.641-1280C>T

Variant names:

• chr20-54167113-G-A
• rs2762941
• NM_000782.5:c.641-1280C>T

Variant summary

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

The NM_000782.5(CYP24A1):​c.641-1280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,002 control chromosomes in the GnomAD database, including 14,302 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 0.43 (14302 hom., cov: 32)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• Publications: 20 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.641-1280C>T		intron_variant	Intron 4 of 11	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.641-1280C>T		intron_variant	Intron 4 of 11	1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64750 AN: 151884 Hom.: 14269 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.426 AC: 64828 AN: 152002 Hom.: 14302 Cov.: 32 AF XY: 0.431 AC XY: 32001 AN XY: 74300

African (AFR) AF: 0.511 AC: 21164 AN: 41440

American (AMR) AF: 0.349 AC: 5339 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1410 AN: 3466

East Asian (EAS) AF: 0.610 AC: 3150 AN: 5166

South Asian (SAS) AF: 0.515 AC: 2480 AN: 4816

European-Finnish (FIN) AF: 0.431 AC: 4548 AN: 10564

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25390 AN: 67954

Other (OTH) AF: 0.414 AC: 873 AN: 2108

Alfa AF: 0.387 Hom.: 14979

Bravo AF: 0.420

Asia WGS AF: 0.552 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.49
DANN	Benign	0.14
PhyloP100		-2.8
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: rs2762941; hg19: chr20-52783652;