dbSNP rs927648: ENSG00000286587:n.155-15385G>C (chr20-54153053-G-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.155-15385G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,012 control chromosomes in the GnomAD database, including 9,225 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 0.33 ( 9225 hom., cov: 32)

Consequence

ENSG00000286587
ENST00000792273.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.81

Publications

2 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3 link	c.*10+4116C>G		intron_variant	Intron 11 of 11		XP_016883181.1	Q07973-1
CYP24A1	XM_047439938.1 link	c.*10+4116C>G		intron_variant	Intron 10 of 10		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000286587	ENST00000792273.1 link	n.155-15385G>C	intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1 link	n.145-15385G>C	intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1 link	n.187-11561G>C	intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1 link	n.126-25336G>C	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

50016

AN:

151894

Hom.:

9219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.305

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

GnomAD4 genome

AF:

0.329

AC:

50041

AN:

152012

Hom.:

9225

Cov.:

AF XY:

0.330

AC XY:

24492

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.478

AC:

19817

AN:

41446

American (AMR)

AF:

0.309

AC:

4723

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

990

AN:

3470

East Asian (EAS)

AF:

0.590

AC:

3046

AN:

5164

South Asian (SAS)

AF:

0.358

AC:

1719

AN:

4808

European-Finnish (FIN)

AF:

0.212

AC:

2246

AN:

10570

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.244

AC:

16604

AN:

67962

Other (OTH)

AF:

0.306

AC:

643

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1642

3284

4925

6567

8209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.287

Hom.:

817

Bravo

AF:

0.342

Asia WGS

AF:

0.429

AC:

1491

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

1.8

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