rs10623012

chr20-54153515-C-CAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000782.5(CYP24A1):c.*1256_*1257insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,900 control chromosomes in the GnomAD database, including 20,450 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (20446 hom., cov: 0)
  • Exomes 𝑓: 0.36 (4 hom.)
• Consequence: CYP24A1 NM_000782.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0410

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 -10 ACMG points.

• BP6: Variant 20-54153515-C-CAT is Benign according to our data. Variant chr20-54153515-C-CAT is described in ClinVar as [Benign]. Clinvar id is 338789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.*1256_*1257insAT		3_prime_UTR_variant	12/12	ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.*1256_*1257insAT		3_prime_UTR_variant	12/12	1	NM_000782.5	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76107 AN: 151740 Hom.: 20421 Cov.: 0

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.364 AC: 16 AN: 44 Hom.: 4 Cov.: 0 AF XY: 0.389 AC XY: 14 AN XY: 36

Gnomad4 FIN exome AF: 0.357

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.502 AC: 76176 AN: 151856 Hom.: 20446 Cov.: 0 AF XY: 0.507 AC XY: 37636 AN XY: 74222

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.483

Alfa AF: 0.444 Hom.: 1921

Bravo AF: 0.505

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Infantile hypercalcemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10623012; hg19: chr20-52770054; COSMIC: COSV53772731; COSMIC: COSV53772731;