20-54156202-T-C

Variant summary

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

The NM_000782.5(CYP24A1):c.*10+967A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,888 control chromosomes in the GnomAD database, including 28,203 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 0.60 (28203 hom., cov: 32)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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 (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.*10+967A>G		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.*10+967A>G		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.*10+967A>G		intron_variant		1
CYP24A1	ENST00000395955.7	c.*10+967A>G		intron_variant		1
CYP24A1	ENST00000460643.1	n.130+967A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91185 AN: 151770 Hom.: 28158 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.601 AC: 91282 AN: 151888 Hom.: 28203 Cov.: 32 AF XY: 0.606 AC XY: 44940 AN XY: 74198

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.570

Alfa AF: 0.541 Hom.: 46651

Bravo AF: 0.596

Asia WGS AF: 0.702 AC: 2439 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	2.1
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs927650; hg19: chr20-52772741;