chr20-54145896-G-T

Variant names:

• chr20-54145896-G-T
• rs6091822
• XM_017027692.3:c.*582C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017027692.3(CYP24A1):​c.*582C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 152,196 control chromosomes in the GnomAD database, including 932 homozygotes. 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 0.091 (932 hom., cov: 33)
• Consequence: CYP24A1 XM_017027692.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 6 publications found

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]

CYP24A1 Gene-Disease associations (from GenCC):

• hypercalcemia, infantile, 1

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• autosomal recessive infantile hypercalcemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000792273.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286587	ENST00000792273.1		n.155-22542G>T		intron	N/A
	ENSG00000286587	ENST00000792274.1		n.145-22542G>T		intron	N/A
	ENSG00000286587	ENST00000792275.1		n.187-18718G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13882 AN: 152078 Hom.: 927 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0521

Gnomad OTH AF: 0.0900

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0913 AC: 13891 AN: 152196 Hom.: 932 Cov.: 33 AF XY: 0.0909 AC XY: 6762 AN XY: 74414

African (AFR) AF: 0.154 AC: 6391 AN: 41494

American (AMR) AF: 0.0535 AC: 818 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1472 AN: 5184

South Asian (SAS) AF: 0.105 AC: 508 AN: 4820

European-Finnish (FIN) AF: 0.0637 AC: 675 AN: 10596

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0521 AC: 3543 AN: 68018

Other (OTH) AF: 0.0928 AC: 196 AN: 2112

Alfa AF: 0.0660 Hom.: 88

Bravo AF: 0.0932

Asia WGS AF: 0.173 AC: 599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.50
DANN	Benign	0.27
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs6091822; hg19: chr20-52762435;