dbSNP rs6097805: ENSG00000286587:n.155-16481A>G (chr20-54151957-A-G) – 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.155-16481A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,992 control chromosomes in the GnomAD database, including 9,296 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 ( 9296 hom., cov: 32)

Consequence

ENSG00000286587
ENST00000792273.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.334

Publications

7 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 = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3 link	c.*10+5212T>C		intron_variant	Intron 11 of 11		XP_016883181.1	Q07973-1
CYP24A1	XM_047439938.1 link	c.*10+5212T>C		intron_variant	Intron 10 of 10		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000286587	ENST00000792273.1 link	n.155-16481A>G	intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1 link	n.145-16481A>G	intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1 link	n.187-12657A>G	intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1 link	n.126-26432A>G	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50202

AN:

151874

Hom.:

9290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.306

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

GnomAD4 genome

AF:

0.330

AC:

50227

AN:

151992

Hom.:

9296

Cov.:

AF XY:

0.331

AC XY:

24578

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.480

AC:

19874

AN:

41392

American (AMR)

AF:

0.309

AC:

4724

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

989

AN:

3470

East Asian (EAS)

AF:

0.592

AC:

3051

AN:

5158

South Asian (SAS)

AF:

0.357

AC:

1716

AN:

4802

European-Finnish (FIN)

AF:

0.214

AC:

2263

AN:

10588

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16725

AN:

67984

Other (OTH)

AF:

0.306

AC:

645

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1600

3201

4801

6402

8002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.294

Hom.:

1431

Bravo

AF:

0.344

Asia WGS

AF:

0.430

AC:

1494

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

1.4

(source)

DANN

Benign

0.80

PhyloP100

0.33

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