20-54160230-G-T

Position:

• chr20-54160230-G-T

Variant summary

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

The NM_000782.5(CYP24A1):​c.991-1107C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,156 control chromosomes in the GnomAD database, including 7,267 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 0.29 (7267 hom., cov: 33)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.991-1107C>A		intron_variant		ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.991-1107C>A		intron_variant		1	NM_000782.5	ENSP00000216862.3
CYP24A1	ENST00000395955.7	c.991-1107C>A		intron_variant		1		ENSP00000379285.3
CYP24A1	ENST00000395954.3	c.565-1107C>A		intron_variant		1		ENSP00000379284.3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44032 AN: 152038 Hom.: 7260 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.290 AC: 44060 AN: 152156 Hom.: 7267 Cov.: 33 AF XY: 0.292 AC XY: 21741 AN XY: 74380

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.266

Alfa AF: 0.246 Hom.: 634

Bravo AF: 0.299

Asia WGS AF: 0.432 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.64

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: rs751089; hg19: chr20-52776769;