dbSNP rs1570670: CYP24A1:c.1236+46T>C (chr20-54158040-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000782.5(CYP24A1):c.1236+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,608,190 control chromosomes in the GnomAD database, including 53,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7332 hom., cov: 33)

Exomes 𝑓: 0.24 ( 46325 hom. )

Consequence

CYP24A1
NM_000782.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.234

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 20-54158040-A-G is Benign according to our data. Variant chr20-54158040-A-G is described in ClinVar as [Benign]. Clinvar id is 1239909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5 link	c.1236+46T>C		intron_variant	Intron 9 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.1236+46T>C		intron_variant	Intron 9 of 11	1	NM_000782.5	ENSP00000216862.3		Q07973-1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44169

AN:

151998

Hom.:

7325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.606

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.263

GnomAD2 exomes

AF:

0.280

AC:

68568

AN:

244564

AF XY:

0.277

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.616

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.240

AC:

348766

AN:

1456074

Hom.:

46325

Cov.:

AF XY:

0.241

AC XY:

174654

AN XY:

724394

show subpopulations

African (AFR)

AF:

0.425

AC:

14202

AN:

33426

American (AMR)

AF:

0.269

AC:

12008

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

6097

AN:

26036

East Asian (EAS)

AF:

0.592

AC:

23465

AN:

39664

South Asian (SAS)

AF:

0.341

AC:

29296

AN:

86012

European-Finnish (FIN)

AF:

0.207

AC:

10299

AN:

49662

Middle Eastern (MID)

AF:

0.209

AC:

1188

AN:

5696

European-Non Finnish (NFE)

AF:

0.213

AC:

236252

AN:

1110736

Other (OTH)

AF:

0.265

AC:

15959

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

12965

25930

38895

51860

64825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.291

AC:

44198

AN:

152116

Hom.:

7332

Cov.:

AF XY:

0.293

AC XY:

21807

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.416

AC:

17257

AN:

41478

American (AMR)

AF:

0.273

AC:

4170

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

794

AN:

3466

East Asian (EAS)

AF:

0.606

AC:

3131

AN:

5164

South Asian (SAS)

AF:

0.355

AC:

1712

AN:

4828

European-Finnish (FIN)

AF:

0.203

AC:

2154

AN:

10600

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14227

AN:

67990

Other (OTH)

AF:

0.264

AC:

558

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1562

3124

4685

6247

7809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.238

Hom.:

2686

Bravo

AF:

0.300

Asia WGS

AF:

0.432

AC:

1503

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.4

(source)

DANN

Benign

0.38

PhyloP100

0.23

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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rs1570670

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