chr20-54153445-C-T

Position:

• chr20-54153445-C-T

Variant summary

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

The XM_017027692.3(CYP24A1):​c.*10+3724G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,002 control chromosomes in the GnomAD database, including 7,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7970 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: CYP24A1 XM_017027692.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71

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=-0.84).
• BP6: Variant 20-54153445-C-T is Benign according to our data. Variant chr20-54153445-C-T is described in ClinVar as [Benign]. Clinvar id is 369356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP24A1	NM_000782.5			downstream_gene_variant		ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8			downstream_gene_variant		1	NM_000782.5	ENSP00000216862	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45611 AN: 151886 Hom.: 7964 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.272

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.300 AC: 45631 AN: 152002 Hom.: 7970 Cov.: 33 AF XY: 0.302 AC XY: 22421 AN XY: 74298

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.273

Alfa AF: 0.193 Hom.: 732

Bravo AF: 0.310

Asia WGS AF: 0.423 AC: 1459 AN: 3454

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Infantile hypercalcemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.63
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4811494; hg19: chr20-52769984;