20-54171651-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000782.5(CYP24A1):c.469C>A(p.Arg157Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,613,754 control chromosomes in the GnomAD database, including 486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 28 hom., cov: 32)

Exomes 𝑓: 0.023 ( 458 hom. )

Consequence

CYP24A1
NM_000782.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.42

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=-0.56).

BP6

Variant 20-54171651-G-T is Benign according to our data. Variant chr20-54171651-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 895614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171651-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.42 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0162 (2458/152092) while in subpopulation NFE AF= 0.0228 (1549/68004). AF 95% confidence interval is 0.0218. There are 28 homozygotes in gnomad4. There are 1110 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5 link	c.469C>A	p.Arg157Arg	synonymous_variant	Exon 3 of 12	ENST00000216862.8	NP_000773.2	Q07973-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP24A1	ENST00000216862.8 link	c.469C>A	p.Arg157Arg	synonymous_variant	Exon 3 of 12	1	NM_000782.5	ENSP00000216862.3	Q07973-1
CYP24A1	ENST00000395955.7 link	c.469C>A	p.Arg157Arg	synonymous_variant	Exon 3 of 11	1		ENSP00000379285.3	Q07973-2
CYP24A1	ENST00000395954.3 link	c.43C>A	p.Arg15Arg	synonymous_variant	Exon 1 of 10	1		ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2445

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00699

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0152

Gnomad FIN

AF:

0.00227

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0163

AC:

4105

AN:

251288

Hom.:

AF XY:

0.0174

AC XY:

2357

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00634

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.0322

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0170

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.0221

Gnomad OTH exome

AF:

0.0225

GnomAD4 exome

AF:

0.0230

AC:

33549

AN:

1461662

Hom.:

458

Cov.:

AF XY:

0.0228

AC XY:

16601

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00807

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.0295

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0177

Gnomad4 FIN exome

AF:

0.00292

Gnomad4 NFE exome

AF:

0.0256

Gnomad4 OTH exome

AF:

0.0253

GnomAD4 genome

AF:

0.0162

AC:

2458

AN:

152092

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1110

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00726

Gnomad4 AMR

AF:

0.0183

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0154

Gnomad4 FIN

AF:

0.00227

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.00644

Hom.:

Bravo

AF:

0.0174

EpiCase

AF:

0.0268

EpiControl

AF:

0.0257

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Apr 12, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CYP24A1: BP4, BP7 -

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hypercalcemia, infantile, 1

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Dec 29, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jun 01, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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