dbSNP rs6097809: CYP24A1:c.*10+198A>G (chr20-54156971-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000782.5(CYP24A1):c.*10+198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 151,864 control chromosomes in the GnomAD database, including 591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.074 ( 591 hom., cov: 32)

Consequence

CYP24A1
NM_000782.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0840

Publications

12 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 20-54156971-T-C is Benign according to our data. Variant chr20-54156971-T-C is described in ClinVar as Benign. ClinVar VariationId is 1252506.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5 link	c.*10+198A>G		intron_variant	Intron 11 of 11	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.*10+198A>G		intron_variant	Intron 11 of 11	1	NM_000782.5	ENSP00000216862.3		Q07973-1

Frequencies

GnomAD3 genomes

AF:

0.0742

AC:

11255

AN:

151746

Hom.:

589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0908

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0543

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0635

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0519

Gnomad OTH

AF:

0.0778

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

GnomAD4 genome

AF:

0.0742

AC:

11269

AN:

151864

Hom.:

591

Cov.:

AF XY:

0.0750

AC XY:

5570

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.0908

AC:

3757

AN:

41370

American (AMR)

AF:

0.0543

AC:

828

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

245

AN:

3472

East Asian (EAS)

AF:

0.297

AC:

1532

AN:

5164

South Asian (SAS)

AF:

0.104

AC:

500

AN:

4788

European-Finnish (FIN)

AF:

0.0635

AC:

668

AN:

10526

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0519

AC:

3527

AN:

67982

Other (OTH)

AF:

0.0808

AC:

170

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

505

1010

1514

2019

2524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0602

Hom.:

Bravo

AF:

0.0744

Asia WGS

AF:

0.177

AC:

614

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 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

-0.88

CADD

Benign

3.4

(source)

DANN

Benign

0.72

PhyloP100

-0.084

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over