XM_017027692.3:c.*10+4357C>A

Variant names:

• chr20-54152812-G-T
• rs6068810
• XM_017027692.3:c.*10+4357C>A

Variant summary

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

The XM_017027692.3(CYP24A1):​c.*10+4357C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 152,216 control chromosomes in the GnomAD database, including 191 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 0.040 (191 hom., cov: 32)
• Consequence: CYP24A1 XM_017027692.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3	c.*10+4357C>A		intron_variant	Intron 11 of 11		XP_016883181.1
CYP24A1	XM_047439938.1	c.*10+4357C>A		intron_variant	Intron 10 of 10		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6132 AN: 152096 Hom.: 192 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0458

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

GnomAD4 genome AF: 0.0403 AC: 6132 AN: 152216 Hom.: 191 Cov.: 32 AF XY: 0.0405 AC XY: 3015 AN XY: 74414

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.0832

Gnomad4 FIN AF: 0.0304

Gnomad4 NFE AF: 0.0470

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0438 Hom.: 161

Bravo AF: 0.0377

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6068810; hg19: chr20-52769351;