dbSNP rs6097801: ENSG00000286587:n.155-17543G>A (chr20-54150895-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.155-17543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,052 control chromosomes in the GnomAD database, including 3,233 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 0.19 ( 3233 hom., cov: 32)

Consequence

ENSG00000286587
ENST00000792273.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.882

Publications

10 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3 link	c.*11-4428C>T		intron_variant	Intron 11 of 11		XP_016883181.1
CYP24A1	XM_047439938.1 link	c.*11-4428C>T		intron_variant	Intron 10 of 10		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000286587	ENST00000792273.1 link	n.155-17543G>A	intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1 link	n.145-17543G>A	intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1 link	n.187-13719G>A	intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1 link	n.125+26978G>A	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29102

AN:

151934

Hom.:

3231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.169

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

GnomAD4 genome

AF:

0.191

AC:

29112

AN:

152052

Hom.:

3233

Cov.:

AF XY:

0.192

AC XY:

14257

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.283

AC:

11718

AN:

41440

American (AMR)

AF:

0.211

AC:

3216

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

535

AN:

3468

East Asian (EAS)

AF:

0.303

AC:

1565

AN:

5170

South Asian (SAS)

AF:

0.135

AC:

650

AN:

4812

European-Finnish (FIN)

AF:

0.120

AC:

1273

AN:

10578

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9625

AN:

67994

Other (OTH)

AF:

0.168

AC:

354

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1157

2314

3471

4628

5785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.158

Hom.:

6595

Bravo

AF:

0.203

Asia WGS

AF:

0.199

AC:

692

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

(source)

DANN

Benign

0.63

PhyloP100

-0.88

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