Genetic Variant CYP24A1:c.990+187A>C (chr20-54162530-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000782.5(CYP24A1):c.990+187A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0067 ( 11 hom., cov: 17)

Exomes 𝑓: 0.00066 ( 3 hom. )

Consequence

CYP24A1
NM_000782.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00666 (568/85302) while in subpopulation AFR AF= 0.0204 (440/21536). AF 95% confidence interval is 0.0189. There are 11 homozygotes in gnomad4. There are 264 alleles in male gnomad4 subpopulation. Median coverage is 17. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5 link	c.990+187A>C		intron_variant	Intron 7 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.990+187A>C	intron_variant	Intron 7 of 11	1	NM_000782.5	ENSP00000216862.3	Q07973-1
CYP24A1	ENST00000395955.7 link	c.990+187A>C	intron_variant	Intron 7 of 10	1		ENSP00000379285.3	Q07973-2
CYP24A1	ENST00000395954.3 link	c.564+187A>C	intron_variant	Intron 5 of 9	1		ENSP00000379284.3	Q07973-3
CYP24A1	ENST00000487593.1 link	n.*50A>C	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00667

AC:

569

AN:

85260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00532

Gnomad AMR

AF:

0.00247

Gnomad ASJ

AF:

0.00250

Gnomad EAS

AF:

0.00583

Gnomad SAS

AF:

0.00558

Gnomad FIN

AF:

0.000437

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00702

GnomAD4 exome

AF:

0.000658

AC:

291

AN:

442136

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

160

AN XY:

235416

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.000614

Gnomad4 ASJ exome

AF:

0.000216

Gnomad4 EAS exome

AF:

0.000462

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.000146

Gnomad4 NFE exome

AF:

0.000246

Gnomad4 OTH exome

AF:

0.000921

GnomAD4 genome

AF:

0.00666

AC:

568

AN:

85302

Hom.:

Cov.:

AF XY:

0.00635

AC XY:

264

AN XY:

41544

show subpopulations

Gnomad4 AFR

AF:

0.0204

Gnomad4 AMR

AF:

0.00247

Gnomad4 ASJ

AF:

0.00250

Gnomad4 EAS

AF:

0.00583

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.000437

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00697

Alfa

AF:

0.00264

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.42

DANN

Benign

0.36

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over