20-54165899-T-G

Position:

• chr20-54165899-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000782.5(CYP24A1):​c.641-66A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 890,584 control chromosomes in the GnomAD database, including 14,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1845 hom., cov: 33)
  • Exomes 𝑓: 0.17 (12169 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.311

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 20-54165899-T-G is Benign according to our data. Variant chr20-54165899-T-G is described in ClinVar as [Benign]. Clinvar id is 1252890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.641-66A>C		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.641-66A>C		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.215-66A>C		intron_variant		1
CYP24A1	ENST00000395955.7	c.641-66A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21495 AN: 152114 Hom.: 1843 Cov.: 33

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.172 AC: 126686 AN: 738352 Hom.: 12169 AF XY: 0.173 AC XY: 68206 AN XY: 393420

Gnomad4 AFR exome AF: 0.0694

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.141 AC: 21502 AN: 152232 Hom.: 1845 Cov.: 33 AF XY: 0.142 AC XY: 10588 AN XY: 74430

Gnomad4 AFR AF: 0.0691

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.140

Alfa AF: 0.157 Hom.: 4109

Bravo AF: 0.139

Asia WGS AF: 0.247 AC: 856 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.80
CADD	Benign	0.69
DANN	Benign	0.82

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: rs4809958; hg19: chr20-52782438;