rs6127118

chr20-54162513-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000782.5(CYP24A1):c.990+204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000613 in 136,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 22)
  • Exomes 𝑓: 0.00064 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP24A1	NM_000782.5	c.990+204C>T		intron_variant		ENST00000216862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP24A1	ENST00000216862.8	c.990+204C>T		intron_variant		1	NM_000782.5	P1
CYP24A1	ENST00000395954.3	c.564+204C>T		intron_variant		1
CYP24A1	ENST00000395955.7	c.990+204C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.000614 AC: 84 AN: 136828 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000662

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00225

Gnomad SAS AF: 0.00149

Gnomad FIN AF: 0.000540

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000285

Gnomad OTH AF: 0.00164

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000645 AC: 236 AN: 366058 Hom.: 1 AF XY: 0.000615 AC XY: 119 AN XY: 193612

Gnomad4 AFR exome AF: 0.000376

Gnomad4 AMR exome AF: 0.00170

Gnomad4 ASJ exome AF: 0.000698

Gnomad4 EAS exome AF: 0.00158

Gnomad4 SAS exome AF: 0.000355

Gnomad4 FIN exome AF: 0.000282

Gnomad4 NFE exome AF: 0.000586

Gnomad4 OTH exome AF: 0.000522

GnomAD4 genome AF: 0.000613 AC: 84 AN: 136924 Hom.: 0 Cov.: 22 AF XY: 0.000802 AC XY: 53 AN XY: 66112

Gnomad4 AFR AF: 0.000660

Gnomad4 AMR AF: 0.00133

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00226

Gnomad4 SAS AF: 0.00149

Gnomad4 FIN AF: 0.000540

Gnomad4 NFE AF: 0.000285

Gnomad4 OTH AF: 0.00162

Alfa AF: 0.166 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.39
Dann	Benign	0.75

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: rs6127118; hg19: chr20-52779052;