Variant chr20-54158040-A-G 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.1236+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,608,190 control chromosomes in the GnomAD database, including 53,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7332 hom., cov: 33)

Exomes 𝑓: 0.24 ( 46325 hom. )

Consequence

CYP24A1
NM_000782.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.234

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:

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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=-0.85).

BP6

Variant 20-54158040-A-G is Benign according to our data. Variant chr20-54158040-A-G is described in ClinVar as [Benign]. Clinvar id is 1239909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 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.1236+46T>C		intron_variant		ENST00000216862.8	NP_000773.2	Q07973-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CYP24A1	ENST00000216862.8 linkuse as main transcript	c.1236+46T>C	intron_variant	1	NM_000782.5	ENSP00000216862.3	Q07973-1
CYP24A1	ENST00000395955.7 linkuse as main transcript	c.1236+46T>C	intron_variant	1		ENSP00000379285.3	Q07973-2
CYP24A1	ENST00000395954.3 linkuse as main transcript	c.810+46T>C	intron_variant	1		ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44169

AN:

151998

Hom.:

7325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.606

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.280

AC:

68568

AN:

244564

Hom.:

11249

AF XY:

0.277

AC XY:

36801

AN XY:

132632

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.616

Gnomad SAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.240

AC:

348766

AN:

1456074

Hom.:

46325

Cov.:

AF XY:

0.241

AC XY:

174654

AN XY:

724394

show subpopulations

Gnomad4 AFR exome

AF:

0.425

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.592

Gnomad4 SAS exome

AF:

0.341

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.291

AC:

44198

AN:

152116

Hom.:

7332

Cov.:

AF XY:

0.293

AC XY:

21807

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.273

Gnomad4 ASJ

AF:

0.229

Gnomad4 EAS

AF:

0.606

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.238

Hom.:

2431

Bravo

AF:

0.300

Asia WGS

AF:

0.432

AC:

1503

AN:

3478

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.4

DANN

Benign

0.38

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