rs6013905

Positions:

• chr20-54164725-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000782.5(CYP24A1):​c.733-162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,678 control chromosomes in the GnomAD database, including 2,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.16 (2180 hom., cov: 31)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.554

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-54164725-T-C is Benign according to our data. Variant chr20-54164725-T-C is described in ClinVar as [Benign]. Clinvar id is 1177674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.733-162A>G		intron_variant		ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.733-162A>G		intron_variant		1	NM_000782.5	ENSP00000216862.3
CYP24A1	ENST00000395955.7	c.733-162A>G		intron_variant		1		ENSP00000379285.3
CYP24A1	ENST00000395954.3	c.307-162A>G		intron_variant		1		ENSP00000379284.3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24634 AN: 151562 Hom.: 2177 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.163 AC: 24658 AN: 151678 Hom.: 2180 Cov.: 31 AF XY: 0.162 AC XY: 12007 AN XY: 74084

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.154

Alfa AF: 0.162 Hom.: 1765

Bravo AF: 0.163

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.81
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs6013905; hg19: chr20-52781264;