rs2296241

Positions:

chr20-54169680-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000782.5(CYP24A1):c.552C>T(p.Ala184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,613,638 control chromosomes in the GnomAD database, including 218,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19925 hom., cov: 33)

Exomes 𝑓: 0.52 ( 198132 hom. )

Consequence

CYP24A1
NM_000782.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.60

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 20-54169680-G-A is Benign according to our data. Variant chr20-54169680-G-A is described in ClinVar as [Benign]. Clinvar id is 338831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54169680-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	NM_000782.5 linkuse as main transcript	c.552C>T	p.Ala184=	synonymous_variant	4/12	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8 linkuse as main transcript	c.552C>T	p.Ala184=	synonymous_variant	4/12	1	NM_000782.5	ENSP00000216862	P1	Q07973-1
CYP24A1	ENST00000395955.7 linkuse as main transcript	c.552C>T	p.Ala184=	synonymous_variant	4/11	1		ENSP00000379285		Q07973-2
CYP24A1	ENST00000395954.3 linkuse as main transcript	c.126C>T	p.Ala42=	synonymous_variant	2/10	1		ENSP00000379284		Q07973-3

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77391

AN:

151898

Hom.:

19911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.521

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.523

GnomAD3 exomes

AF:

0.491

AC:

123351

AN:

251276

Hom.:

30995

AF XY:

0.493

AC XY:

66951

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.497

Gnomad AMR exome

AF:

0.389

Gnomad ASJ exome

AF:

0.622

Gnomad EAS exome

AF:

0.419

Gnomad SAS exome

AF:

0.440

Gnomad FIN exome

AF:

0.510

Gnomad NFE exome

AF:

0.530

Gnomad OTH exome

AF:

0.526

GnomAD4 exome

AF:

0.519

AC:

758066

AN:

1461622

Hom.:

198132

Cov.:

106

AF XY:

0.518

AC XY:

376380

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.624

Gnomad4 EAS exome

AF:

0.439

Gnomad4 SAS exome

AF:

0.440

Gnomad4 FIN exome

AF:

0.512

Gnomad4 NFE exome

AF:

0.530

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.509

AC:

77450

AN:

152016

Hom.:

19925

Cov.:

AF XY:

0.506

AC XY:

37623

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.500

Gnomad4 AMR

AF:

0.463

Gnomad4 ASJ

AF:

0.628

Gnomad4 EAS

AF:

0.408

Gnomad4 SAS

AF:

0.436

Gnomad4 FIN

AF:

0.521

Gnomad4 NFE

AF:

0.531

Gnomad4 OTH

AF:

0.523

Alfa

AF:

0.529

Hom.:

55654

Bravo

AF:

0.504

Asia WGS

AF:

0.441

AC:

1534

AN:

3478

EpiCase

AF:

0.548

EpiControl

AF:

0.541

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypercalcemia, infantile, 1

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 06, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	p.Ala184Ala in exon 4 of CYP24A1: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 53.00% (35334/6666 8) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs2296241). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.1

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over