rs2209314

Variant names:

• chr20-54162422-T-C
• rs2209314
• NM_000782.5:c.990+295A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 32 publications found

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]

CYP24A1 Gene-Disease associations (from GenCC):

• hypercalcemia, infantile, 1

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• autosomal recessive infantile hypercalcemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.990+295A>G		intron_variant	Intron 7 of 11	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.990+295A>G		intron_variant	Intron 7 of 11	1	NM_000782.5	ENSP00000216862.3

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

African (AFR) AF: 0.0953 AC: 3457 AN: 36286

American (AMR) AF: 0.230 AC: 3193 AN: 13878

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 887 AN: 3272

East Asian (EAS) AF: 0.446 AC: 1980 AN: 4440

South Asian (SAS) AF: 0.374 AC: 1593 AN: 4256

European-Finnish (FIN) AF: 0.323 AC: 3125 AN: 9678

Middle Eastern (MID) AF: 0.259 AC: 72 AN: 278

European-Non Finnish (NFE) AF: 0.260 AC: 16495 AN: 63536

Other (OTH) AF: 0.253 AC: 475 AN: 1874

Alfa AF: 0.227 Hom.: 6746

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

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.47
PhyloP100		-0.010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2209314; hg19: chr20-52778961;