20-54164552-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000782.5(CYP24A1):c.744G>A(p.Thr248Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,614,026 control chromosomes in the GnomAD database, including 12,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 1008 hom., cov: 32)

Exomes 𝑓: 0.11 ( 11261 hom. )

Consequence

CYP24A1
NM_000782.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.32

Publications

84 publications found

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 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

CYP24A1 links:

ENSG00000286587 (HGNC:):

ENSG00000286587 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 20-54164552-C-T is Benign according to our data. Variant chr20-54164552-C-T is described in ClinVar as Benign. ClinVar VariationId is 338825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5 link	c.744G>A	p.Thr248Thr	synonymous_variant	Exon 6 of 12	ENST00000216862.8	NP_000773.2	Q07973-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8 link	c.744G>A	p.Thr248Thr	synonymous_variant	Exon 6 of 12	1	NM_000782.5	ENSP00000216862.3		Q07973-1

Frequencies

GnomAD3 genomes

AF:

0.0948

AC:

14411

AN:

152056

Hom.:

1007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.0967

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.0652

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.103

GnomAD2 exomes

AF:

0.124

AC:

31139

AN:

251404

AF XY:

0.126

show subpopulations

Gnomad AFR exome

AF:

0.0398

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.0734

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.113

AC:

165407

AN:

1461852

Hom.:

11261

Cov.:

AF XY:

0.115

AC XY:

83343

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0385

AC:

1290

AN:

33480

American (AMR)

AF:

0.103

AC:

4619

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

3056

AN:

26134

East Asian (EAS)

AF:

0.380

AC:

15074

AN:

39698

South Asian (SAS)

AF:

0.158

AC:

13640

AN:

86258

European-Finnish (FIN)

AF:

0.0760

AC:

4058

AN:

53418

Middle Eastern (MID)

AF:

0.129

AC:

741

AN:

5766

European-Non Finnish (NFE)

AF:

0.104

AC:

115657

AN:

1111984

Other (OTH)

AF:

0.120

AC:

7272

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

9915

19830

29746

39661

49576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4464

8928

13392

17856

22320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0947

AC:

14415

AN:

152174

Hom.:

1008

Cov.:

AF XY:

0.0958

AC XY:

7129

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0408

AC:

1696

AN:

41528

American (AMR)

AF:

0.0969

AC:

1482

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

354

AN:

3468

East Asian (EAS)

AF:

0.366

AC:

1885

AN:

5156

South Asian (SAS)

AF:

0.172

AC:

831

AN:

4822

European-Finnish (FIN)

AF:

0.0652

AC:

690

AN:

10584

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7065

AN:

68002

Other (OTH)

AF:

0.103

AC:

217

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

642

1284

1926

2568

3210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.104

Hom.:

3874

Bravo

AF:

0.0945

EpiCase

AF:

0.100

EpiControl

AF:

0.110

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypercalcemia, infantile, 1

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.23

(source)

DANN

Benign

0.65

PhyloP100

-4.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over