Genetic Variant ENST00000792273.1:n.155-15626G>T (chr20-54152812-G-T) – 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.155-15626G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 152,216 control chromosomes in the GnomAD database, including 191 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 0.040 ( 191 hom., cov: 32)

Consequence

ENSG00000286587
ENST00000792273.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Publications

8 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3 link	c.*10+4357C>A		intron_variant	Intron 11 of 11		XP_016883181.1	Q07973-1
CYP24A1	XM_047439938.1 link	c.*10+4357C>A		intron_variant	Intron 10 of 10		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000286587	ENST00000792273.1 link	n.155-15626G>T	intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1 link	n.145-15626G>T	intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1 link	n.187-11802G>T	intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1 link	n.126-25577G>T	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0403

AC:

6132

AN:

152096

Hom.:

192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0311

Gnomad ASJ

AF:

0.0877

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0833

Gnomad FIN

AF:

0.0304

Gnomad MID

AF:

0.0541

Gnomad NFE

AF:

0.0470

Gnomad OTH

AF:

0.0458

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

GnomAD4 genome

AF:

0.0403

AC:

6132

AN:

152216

Hom.:

191

Cov.:

AF XY:

0.0405

AC XY:

3015

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0143

AC:

595

AN:

41534

American (AMR)

AF:

0.0310

AC:

474

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0877

AC:

304

AN:

3466

East Asian (EAS)

AF:

0.140

AC:

720

AN:

5156

South Asian (SAS)

AF:

0.0832

AC:

401

AN:

4820

European-Finnish (FIN)

AF:

0.0304

AC:

322

AN:

10608

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0470

AC:

3200

AN:

68014

Other (OTH)

AF:

0.0473

AC:

100

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

288

576

863

1151

1439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0431

Hom.:

209

Bravo

AF:

0.0377

Asia WGS

AF:

0.109

AC:

380

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.1

(source)

DANN

Benign

0.68

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