20-54145941-G-A

Position:

• chr20-54145941-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017027692.3(CYP24A1):​c.*537C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,124 control chromosomes in the GnomAD database, including 8,746 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 0.34 (8746 hom., cov: 33)
• Consequence: CYP24A1 XM_017027692.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	XM_017027692.3	c.*537C>T		3_prime_UTR_variant	12/12		XP_016883181.1
CYP24A1	XM_047439938.1	c.*537C>T		3_prime_UTR_variant	11/11		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51147 AN: 152006 Hom.: 8743 Cov.: 33

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.336 AC: 51178 AN: 152124 Hom.: 8746 Cov.: 33 AF XY: 0.343 AC XY: 25519 AN XY: 74376

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.321

Alfa AF: 0.309 Hom.: 3414

Bravo AF: 0.335

Asia WGS AF: 0.412 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2585413; hg19: chr20-52762480;