dbSNP rs8118441: ENSG00000286587:n.155-18592T>A (chr20-54149846-T-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.155-18592T>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 152,136 control chromosomes in the GnomAD database, including 3,214 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 ( 3214 hom., cov: 32)

Consequence

ENSG00000286587
ENST00000792273.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.136

Publications

1 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3 link	c.*11-3379A>T		intron_variant	Intron 11 of 11		XP_016883181.1	Q07973-1
CYP24A1	XM_047439938.1 link	c.*11-3379A>T		intron_variant	Intron 10 of 10		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000286587	ENST00000792273.1 link	n.155-18592T>A	intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1 link	n.145-18592T>A	intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1 link	n.187-14768T>A	intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1 link	n.125+25929T>A	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29019

AN:

152020

Hom.:

3212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.121

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:

29028

AN:

152136

Hom.:

3214

Cov.:

AF XY:

0.191

AC XY:

14217

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.281

AC:

11642

AN:

41484

American (AMR)

AF:

0.210

AC:

3206

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

535

AN:

3468

East Asian (EAS)

AF:

0.301

AC:

1556

AN:

5168

South Asian (SAS)

AF:

0.135

AC:

650

AN:

4816

European-Finnish (FIN)

AF:

0.121

AC:

1282

AN:

10608

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9627

AN:

67984

Other (OTH)

AF:

0.168

AC:

354

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1178

2356

3534

4712

5890

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:

0.171

Hom.:

285

Bravo

AF:

0.202

Asia WGS

AF:

0.201

AC:

700

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.0

(source)

DANN

Benign

0.81

PhyloP100

-0.14

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