rs6127112

Positions:

• chr20-54145114-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.*1364C>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 0.0852 in 152,018 control chromosomes in the GnomAD database, including 672 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 0.085 (672 hom., cov: 31)
• Consequence: CYP24A1 XM_017027692.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	XM_017027692.3	c.*1364C>T		3_prime_UTR_variant	12/12		XP_016883181.1
CYP24A1	XM_047439938.1	c.*1364C>T		3_prime_UTR_variant	11/11		XP_047295894.1
		n.54145114G>A		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12947 AN: 151900 Hom.: 674 Cov.: 31

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.0906

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

GnomAD4 genome AF: 0.0852 AC: 12950 AN: 152018 Hom.: 672 Cov.: 31 AF XY: 0.0858 AC XY: 6378 AN XY: 74330

Gnomad4 AFR AF: 0.0461

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.0610

Gnomad4 NFE AF: 0.0995

Gnomad4 OTH AF: 0.0916

Alfa AF: 0.100 Hom.: 516

Bravo AF: 0.0812

Asia WGS AF: 0.168 AC: 582 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6127112; hg19: chr20-52761653;