dbSNP rs2585413: CYP24A1:c.*537C>T (chr20-54145941-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_017027692.3(CYP24A1):c.*537C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,124 control chromosomes in the GnomAD database, including 8,746 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 8746 hom., cov: 33)

Consequence

CYP24A1
XM_017027692.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0400

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3 link	c.*537C>T		3_prime_UTR_variant	Exon 12 of 12		XP_016883181.1
CYP24A1	XM_047439938.1 link	c.*537C>T		3_prime_UTR_variant	Exon 11 of 11		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000286587	ENST00000792273.1 link	n.155-22497G>A	intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1 link	n.145-22497G>A	intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1 link	n.187-18673G>A	intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1 link	n.125+22024G>A	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

51147

AN:

152006

Hom.:

8743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.395

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.318

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

GnomAD4 genome

AF:

0.336

AC:

51178

AN:

152124

Hom.:

8746

Cov.:

AF XY:

0.343

AC XY:

25519

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.395

AC:

16377

AN:

41490

American (AMR)

AF:

0.324

AC:

4956

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1201

AN:

3470

East Asian (EAS)

AF:

0.400

AC:

2068

AN:

5170

South Asian (SAS)

AF:

0.425

AC:

2051

AN:

4830

European-Finnish (FIN)

AF:

0.343

AC:

3622

AN:

10550

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19877

AN:

68012

Other (OTH)

AF:

0.321

AC:

678

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1773

3546

5319

7092

8865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.309

Hom.:

3857

Bravo

AF:

0.335

Asia WGS

AF:

0.412

AC:

1435

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.3

(source)

DANN

Benign

0.47

PhyloP100

0.040

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over