dbSNP rs10623012: CYP24A1:c.*1256_*1257insAT (chr20-54153515-C-CAT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000782.5(CYP24A1):c.*1256_*1257insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 20446 hom., cov: 0)

Exomes 𝑓: 0.36 ( 4 hom. )

Consequence

CYP24A1
NM_000782.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0410

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, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
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 -10 ACMG points.

BP6

Variant 20-54153515-C-CAT is Benign according to our data. Variant chr20-54153515-C-CAT is described in ClinVar as Benign. ClinVar VariationId is 338789.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP24A1	NM_000782.5	MANE Select	c.1256_1257insAT	3_prime_UTR	Exon 12 of 12	NP_000773.2	Q07973-1
CYP24A1	NM_001424340.1		c.1276_1277insAT	3_prime_UTR	Exon 12 of 12	NP_001411269.1	Q07973-1
CYP24A1	NM_001424341.1		c.1428_1429insAT	3_prime_UTR	Exon 12 of 12	NP_001411270.1	Q07973-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.1256_1257insAT	3_prime_UTR	Exon 12 of 12	ENSP00000216862.3	Q07973-1
CYP24A1	ENST00000869535.1		c.1428_1429insAT	3_prime_UTR	Exon 12 of 12	ENSP00000539594.1
CYP24A1	ENST00000869536.1		c.1276_1277insAT	3_prime_UTR	Exon 12 of 12	ENSP00000539595.1

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76107

AN:

151740

Hom.:

20421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.685

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.475

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.478

GnomAD4 exome

AF:

0.364

AC:

AN:

Hom.:

Cov.:

AF XY:

0.389

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.357

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.502

AC:

76176

AN:

151856

Hom.:

20446

Cov.:

AF XY:

0.507

AC XY:

37636

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.685

AC:

28367

AN:

41398

American (AMR)

AF:

0.430

AC:

6560

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

1649

AN:

3468

East Asian (EAS)

AF:

0.694

AC:

3589

AN:

5174

South Asian (SAS)

AF:

0.654

AC:

3156

AN:

4822

European-Finnish (FIN)

AF:

0.435

AC:

4574

AN:

10506

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.395

AC:

26837

AN:

67918

Other (OTH)

AF:

0.483

AC:

1019

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1871

3742

5613

7484

9355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.444

Hom.:

1921

Bravo

AF:

0.505

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Infantile hypercalcemia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.041

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over