rs1570670

chr20-54158040-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000782.5(CYP24A1):c.1236+46T>C 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 1,608,190 control chromosomes in the GnomAD database, including 53,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7332 hom., cov: 33)
  • Exomes 𝑓: 0.24 (46325 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.234

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-54158040-A-G is Benign according to our data. Variant chr20-54158040-A-G is described in ClinVar as [Benign]. Clinvar id is 1239909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.1236+46T>C		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.1236+46T>C		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.810+46T>C		intron_variant		1
CYP24A1	ENST00000395955.7	c.1236+46T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44169 AN: 151998 Hom.: 7325 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.263

GnomAD3 exomes AF: 0.280 AC: 68568 AN: 244564 Hom.: 11249 AF XY: 0.277 AC XY: 36801 AN XY: 132632

Gnomad AFR exome AF: 0.418

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.616

Gnomad SAS exome AF: 0.337

Gnomad FIN exome AF: 0.202

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.240 AC: 348766 AN: 1456074 Hom.: 46325 Cov.: 33 AF XY: 0.241 AC XY: 174654 AN XY: 724394

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.592

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.291 AC: 44198 AN: 152116 Hom.: 7332 Cov.: 33 AF XY: 0.293 AC XY: 21807 AN XY: 74376

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.264

Alfa AF: 0.238 Hom.: 2431

Bravo AF: 0.300

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.85
Cadd	Benign	2.4
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: rs1570670; hg19: chr20-52774579; COSMIC: COSV53772725; COSMIC: COSV53772725;