rs2181874

chr20-54167939-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.640+1653C>T		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.640+1653C>T		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.214+1653C>T		intron_variant		1
CYP24A1	ENST00000395955.7	c.640+1653C>T		intron_variant		1

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

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.314

Alfa AF: 0.262 Hom.: 7686

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2181874; hg19: chr20-52784478;