chr20-54164712-G-C

Position:

• chr20-54164712-G-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.733-149C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,476,674 control chromosomes in the GnomAD database, including 60,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10483 hom., cov: 31)
  • Exomes 𝑓: 0.27 (49827 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.28

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=-0.91).
• BP6: Variant 20-54164712-G-C is Benign according to our data. Variant chr20-54164712-G-C is described in ClinVar as [Benign]. Clinvar id is 1297888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54164712-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.733-149C>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.733-149C>G		intron_variant		1	NM_000782.5	ENSP00000216862.3
CYP24A1	ENST00000395955.7	c.733-149C>G		intron_variant		1		ENSP00000379285.3
CYP24A1	ENST00000395954.3	c.307-149C>G		intron_variant		1		ENSP00000379284.3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52667 AN: 151676 Hom.: 10454 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.317

GnomAD4 exome AF: 0.266 AC: 352256 AN: 1324880 Hom.: 49827 AF XY: 0.267 AC XY: 175319 AN XY: 656012

Gnomad4 AFR exome AF: 0.566

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.340

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.347 AC: 52727 AN: 151794 Hom.: 10483 Cov.: 31 AF XY: 0.348 AC XY: 25840 AN XY: 74150

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.323

Alfa AF: 0.154 Hom.: 286

Bravo AF: 0.348

Asia WGS AF: 0.327 AC: 1137 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 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.052
DANN	Benign	0.40

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: rs2762939; hg19: chr20-52781251;