rs6091828

chr20-54162671-G-T

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.990+46C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 1,222,902 control chromosomes in the GnomAD database, including 1,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.071 (612 hom., cov: 30)
  • Exomes 𝑓: 0.039 (1348 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0480

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=-0.93).
• BP6: Variant 20-54162671-G-T is Benign according to our data. Variant chr20-54162671-G-T is described in ClinVar as [Benign]. Clinvar id is 1174391.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.990+46C>A		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.990+46C>A		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.564+46C>A		intron_variant		1
CYP24A1	ENST00000395955.7	c.990+46C>A		intron_variant		1
CYP24A1	ENST00000487593.1	n.289C>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10485 AN: 147782 Hom.: 609 Cov.: 30

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.0311

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0519

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0707

GnomAD3 exomes AF: 0.0559 AC: 14037 AN: 251292 Hom.: 609 AF XY: 0.0553 AC XY: 7510 AN XY: 135830

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.0949

Gnomad ASJ exome AF: 0.0355

Gnomad EAS exome AF: 0.0294

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.0383

Gnomad NFE exome AF: 0.0287

Gnomad OTH exome AF: 0.0462

GnomAD4 exome AF: 0.0386 AC: 41484 AN: 1075004 Hom.: 1348 Cov.: 15 AF XY: 0.0402 AC XY: 22213 AN XY: 552892

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0912

Gnomad4 ASJ exome AF: 0.0370

Gnomad4 EAS exome AF: 0.0231

Gnomad4 SAS exome AF: 0.0984

Gnomad4 FIN exome AF: 0.0364

Gnomad4 NFE exome AF: 0.0263

Gnomad4 OTH exome AF: 0.0442

GnomAD4 genome AF: 0.0711 AC: 10513 AN: 147898 Hom.: 612 Cov.: 30 AF XY: 0.0735 AC XY: 5304 AN XY: 72152

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0880

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.0312

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0280

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0499 Hom.: 95

Bravo AF: 0.0763

Asia WGS AF: 0.104 AC: 363 AN: 3476

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	-0.93
Cadd	Benign	1.1
Dann	Benign	0.53

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: rs6091828; hg19: chr20-52779210; COSMIC: COSV53774592;