rs6127119

Positions:

• chr20-54162543-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000782.5(CYP24A1):​c.990+174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 593,070 control chromosomes in the GnomAD database, including 20,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4804 hom., cov: 25)
  • Exomes 𝑓: 0.24 (15625 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-54162543-C-T is Benign according to our data. Variant chr20-54162543-C-T is described in ClinVar as [Benign]. Clinvar id is 1282351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.990+174G>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.990+174G>A		intron_variant		1	NM_000782.5	ENSP00000216862	P1
CYP24A1	ENST00000395954.3	c.564+174G>A		intron_variant		1		ENSP00000379284
CYP24A1	ENST00000395955.7	c.990+174G>A		intron_variant		1		ENSP00000379285
CYP24A1	ENST00000487593.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 34232 AN: 139646 Hom.: 4795 Cov.: 25

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.244 AC: 110636 AN: 453310 Hom.: 15625 Cov.: 4 AF XY: 0.246 AC XY: 59541 AN XY: 241660

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.245 AC: 34280 AN: 139760 Hom.: 4804 Cov.: 25 AF XY: 0.245 AC XY: 16566 AN XY: 67590

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.240

Alfa AF: 0.237 Hom.: 2139

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.71

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: rs6127119; hg19: chr20-52779082;