rs2181874

Variant names:

• chr20-54167939-G-A
• rs2181874
• NM_000782.5:c.640+1653C>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.640+1653C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,998 control chromosomes in the GnomAD database, including 7,406 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 0.30 (7406 hom., cov: 32)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 25 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.640+1653C>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.640+1653C>T		intron_variant	Intron 4 of 11	1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46029 AN: 151880 Hom.: 7391 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.303 AC: 46069 AN: 151998 Hom.: 7406 Cov.: 32 AF XY: 0.307 AC XY: 22805 AN XY: 74286

African (AFR) AF: 0.403 AC: 16695 AN: 41424

American (AMR) AF: 0.312 AC: 4770 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1212 AN: 5168

South Asian (SAS) AF: 0.408 AC: 1965 AN: 4814

European-Finnish (FIN) AF: 0.265 AC: 2799 AN: 10572

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16632 AN: 67946

Other (OTH) AF: 0.314 AC: 663 AN: 2110

Alfa AF: 0.265 Hom.: 11903

Bravo AF: 0.306

Asia WGS AF: 0.351 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.48
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2181874; hg19: chr20-52784478;