rs2209314

chr20-54162422-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.990+295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 138,326 control chromosomes in the GnomAD database, including 3,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (3842 hom., cov: 25)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0100

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=-0.9).
• BP6: Variant 20-54162422-T-C is Benign according to our data. Variant chr20-54162422-T-C is described in ClinVar as [Benign]. Clinvar id is 1239841.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.990+295A>G		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.990+295A>G		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.564+295A>G		intron_variant		1
CYP24A1	ENST00000395955.7	c.990+295A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 31471 AN: 138226 Hom.: 3844 Cov.: 25

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.227 AC: 31467 AN: 138326 Hom.: 3842 Cov.: 25 AF XY: 0.232 AC XY: 15663 AN XY: 67462

Gnomad4 AFR AF: 0.0953

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.253

Alfa AF: 0.210 Hom.: 925

Bravo AF: 0.195

Asia WGS AF: 0.342 AC: 1187 AN: 3474

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

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.21
Dann	Benign	0.47

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: rs2209314; hg19: chr20-52778961;