Genetic Variant CYP24A1:c.1236+146G>A (chr20-54157940-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000782.5(CYP24A1):c.1236+146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,384,664 control chromosomes in the GnomAD database, including 12,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2933 hom., cov: 33)

Exomes 𝑓: 0.12 ( 9676 hom. )

Consequence

CYP24A1
NM_000782.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.752

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 20-54157940-C-T is Benign according to our data. Variant chr20-54157940-C-T is described in ClinVar as [Benign]. Clinvar id is 1236993.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5 link	c.1236+146G>A		intron_variant	Intron 9 of 11	ENST00000216862.8	NP_000773.2	Q07973-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP24A1	ENST00000216862.8 link	c.1236+146G>A	intron_variant	Intron 9 of 11	1	NM_000782.5	ENSP00000216862.3	Q07973-1
CYP24A1	ENST00000395955.7 link	c.1236+146G>A	intron_variant	Intron 9 of 10	1		ENSP00000379285.3	Q07973-2
CYP24A1	ENST00000395954.3 link	c.810+146G>A	intron_variant	Intron 7 of 9	1		ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26294

AN:

152110

Hom.:

2932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.0991

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.138

GnomAD4 exome

AF:

0.116

AC:

142603

AN:

1232436

Hom.:

9676

AF XY:

0.115

AC XY:

70439

AN XY:

611262

show subpopulations

Gnomad4 AFR exome

AF:

0.286

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.0938

Gnomad4 EAS exome

AF:

0.309

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.173

AC:

26309

AN:

152228

Hom.:

2933

Cov.:

AF XY:

0.175

AC XY:

12989

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.0991

Gnomad4 EAS

AF:

0.303

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.103

Hom.:

280

Bravo

AF:

0.183

Asia WGS

AF:

0.196

AC:

683

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.4

DANN

Benign

0.67

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