Genetic Variant ENSG00000286587:n.155-16586T>C (chr20-54151852-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000792273.1(ENSG00000286587):n.155-16586T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,034 control chromosomes in the GnomAD database, including 2,349 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 0.17 ( 2349 hom., cov: 32)

Consequence

ENSG00000286587
ENST00000792273.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.165

Publications

17 publications found

Variant links:

Genes affected

ENSG00000286587 (HGNC:):

ENSG00000286587 links:

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:

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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3 link	c.*10+5317A>G		intron_variant	Intron 11 of 11		XP_016883181.1
CYP24A1	XM_047439938.1 link	c.*10+5317A>G		intron_variant	Intron 10 of 10		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000286587	ENST00000792273.1 link	n.155-16586T>C	intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1 link	n.145-16586T>C	intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1 link	n.187-12762T>C	intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1 link	n.126-26537T>C	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25875

AN:

151916

Hom.:

2345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.172

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

GnomAD4 genome

AF:

0.170

AC:

25920

AN:

152034

Hom.:

2349

Cov.:

AF XY:

0.176

AC XY:

13049

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.200

AC:

8282

AN:

41408

American (AMR)

AF:

0.121

AC:

1850

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

655

AN:

3472

East Asian (EAS)

AF:

0.101

AC:

521

AN:

5168

South Asian (SAS)

AF:

0.298

AC:

1432

AN:

4812

European-Finnish (FIN)

AF:

0.222

AC:

2355

AN:

10596

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10277

AN:

67980

Other (OTH)

AF:

0.177

AC:

373

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1083

2166

3250

4333

5416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.157

Hom.:

3582

Bravo

AF:

0.161

Asia WGS

AF:

0.224

AC:

778

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.5

(source)

DANN

Benign

0.55

PhyloP100

-0.17

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