dbSNP rs8124792: ENSG00000286587:n.155-18170G>A (chr20-54150268-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 ENST00000792273.1(ENSG00000286587):n.155-18170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,174 control chromosomes in the GnomAD database, including 650 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 0.079 ( 650 hom., cov: 32)

Consequence

ENSG00000286587
ENST00000792273.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.341

Publications

18 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3 link	c.*11-3801C>T		intron_variant	Intron 11 of 11		XP_016883181.1	Q07973-1
CYP24A1	XM_047439938.1 link	c.*11-3801C>T		intron_variant	Intron 10 of 10		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000286587	ENST00000792273.1 link	n.155-18170G>A	intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1 link	n.145-18170G>A	intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1 link	n.187-14346G>A	intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1 link	n.125+26351G>A	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0792

AC:

12049

AN:

152056

Hom.:

647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0500

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0634

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0519

Gnomad OTH

AF:

0.0829

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

GnomAD4 genome

AF:

0.0792

AC:

12056

AN:

152174

Hom.:

650

Cov.:

AF XY:

0.0794

AC XY:

5908

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.113

AC:

4670

AN:

41504

American (AMR)

AF:

0.0498

AC:

761

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

245

AN:

3472

East Asian (EAS)

AF:

0.279

AC:

1448

AN:

5184

South Asian (SAS)

AF:

0.106

AC:

510

AN:

4822

European-Finnish (FIN)

AF:

0.0634

AC:

671

AN:

10588

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0519

AC:

3527

AN:

68002

Other (OTH)

AF:

0.0859

AC:

181

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

581

1162

1744

2325

2906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0636

Hom.:

1277

Bravo

AF:

0.0793

Asia WGS

AF:

0.169

AC:

587

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.5

(source)

DANN

Benign

0.61

PhyloP100

0.34

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