chr20-54169867-T-C

Variant names:

• chr20-54169867-T-C
• rs2245153
• NM_000782.5:c.544-179A>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.544-179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,222 control chromosomes in the GnomAD database, including 3,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (3937 hom., cov: 33)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47
• Publications: 20 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=-0.91).
• BP6: Variant 20-54169867-T-C is Benign according to our data. Variant chr20-54169867-T-C is described in ClinVar as Benign. ClinVar VariationId is 1243790.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.544-179A>G		intron_variant	Intron 3 of 11	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.544-179A>G		intron_variant	Intron 3 of 11	1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32999 AN: 152104 Hom.: 3924 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.217 AC: 33057 AN: 152222 Hom.: 3937 Cov.: 33 AF XY: 0.212 AC XY: 15789 AN XY: 74414

African (AFR) AF: 0.306 AC: 12697 AN: 41522

American (AMR) AF: 0.158 AC: 2416 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1076 AN: 5188

South Asian (SAS) AF: 0.222 AC: 1073 AN: 4830

European-Finnish (FIN) AF: 0.119 AC: 1260 AN: 10610

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13051 AN: 67996

Other (OTH) AF: 0.211 AC: 447 AN: 2114

Alfa AF: 0.202 Hom.: 9872

Bravo AF: 0.223

Asia WGS AF: 0.246 AC: 852 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

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	-0.91
CADD	Benign	0.53
DANN	Benign	0.25
PhyloP100		-1.5
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: rs2245153; hg19: chr20-52786406;