rs4809960

chr20-54169534-T-C

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.640+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,611,864 control chromosomes in the GnomAD database, including 45,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3455 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42057 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.83

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=-0.91).
• BP6: Variant 20-54169534-T-C is Benign according to our data. Variant chr20-54169534-T-C is described in ClinVar as [Benign]. Clinvar id is 1226435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.640+58A>G		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.640+58A>G		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.214+58A>G		intron_variant		1
CYP24A1	ENST00000395955.7	c.640+58A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30758 AN: 152088 Hom.: 3450 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.238 AC: 347043 AN: 1459658 Hom.: 42057 AF XY: 0.239 AC XY: 173511 AN XY: 726140

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.202 AC: 30772 AN: 152206 Hom.: 3455 Cov.: 32 AF XY: 0.200 AC XY: 14861 AN XY: 74418

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.216

Alfa AF: 0.236 Hom.: 6011

Bravo AF: 0.201

Asia WGS AF: 0.242 AC: 841 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 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.039
Dann	Benign	0.29

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: rs4809960; hg19: chr20-52786073; COSMIC: COSV53774641; COSMIC: COSV53774641;