Variant rs6091828 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000782.5(CYP24A1):c.990+46C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 1,222,902 control chromosomes in the GnomAD database, including 1,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 612 hom., cov: 30)

Exomes 𝑓: 0.039 ( 1348 hom. )

Consequence

CYP24A1
NM_000782.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0480

Variant links:

Genes affected

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 links:

CYP24A1 (HGNC:):

CYP24A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 20-54162671-G-T is Benign according to our data. Variant chr20-54162671-G-T is described in ClinVar as [Benign]. Clinvar id is 1174391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	NM_000782.5 linkuse as main transcript	c.990+46C>A		intron_variant		ENST00000216862.8	NP_000773.2	Q07973-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYP24A1	ENST00000216862.8 linkuse as main transcript	c.990+46C>A	intron_variant		1	NM_000782.5	ENSP00000216862.3	Q07973-1
CYP24A1	ENST00000395955.7 linkuse as main transcript	c.990+46C>A	intron_variant		1		ENSP00000379285.3	Q07973-2
CYP24A1	ENST00000395954.3 linkuse as main transcript	c.564+46C>A	intron_variant		1		ENSP00000379284.3	Q07973-3
CYP24A1	ENST00000487593.1 linkuse as main transcript	n.289C>A	non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0709

AC:

10485

AN:

147782

Hom.:

609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0882

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.0311

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.0519

Gnomad NFE

AF:

0.0279

Gnomad OTH

AF:

0.0707

GnomAD3 exomes

AF:

0.0559

AC:

14037

AN:

251292

Hom.:

609

AF XY:

0.0553

AC XY:

7510

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.0949

Gnomad ASJ exome

AF:

0.0355

Gnomad EAS exome

AF:

0.0294

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0383

Gnomad NFE exome

AF:

0.0287

Gnomad OTH exome

AF:

0.0462

GnomAD4 exome

AF:

0.0386

AC:

41484

AN:

1075004

Hom.:

1348

Cov.:

AF XY:

0.0402

AC XY:

22213

AN XY:

552892

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.0912

Gnomad4 ASJ exome

AF:

0.0370

Gnomad4 EAS exome

AF:

0.0231

Gnomad4 SAS exome

AF:

0.0984

Gnomad4 FIN exome

AF:

0.0364

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0442

GnomAD4 genome

AF:

0.0711

AC:

10513

AN:

147898

Hom.:

612

Cov.:

AF XY:

0.0735

AC XY:

5304

AN XY:

72152

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.0880

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.0312

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0406

Gnomad4 NFE

AF:

0.0280

Gnomad4 OTH

AF:

0.0733

Alfa

AF:

0.0499

Hom.:

Bravo

AF:

0.0763

Asia WGS

AF:

0.104

AC:

363

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over