chr20-54152916-A-G

Variant names:

• chr20-54152916-A-G
• rs6097807
• ENST00000792273.1:n.155-15522A>G

Variant summary

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

The ENST00000792273.1(ENSG00000286587):​n.155-15522A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,090 control chromosomes in the GnomAD database, including 9,231 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 0.33 (9231 hom., cov: 32)
• Consequence: ENSG00000286587 ENST00000792273.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 6 publications found

Genes affected

ENSG00000286587 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286587	ENST00000792273.1		n.155-15522A>G		intron	N/A
	ENSG00000286587	ENST00000792274.1		n.145-15522A>G		intron	N/A
	ENSG00000286587	ENST00000792275.1		n.187-11698A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50047 AN: 151972 Hom.: 9225 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.329 AC: 50072 AN: 152090 Hom.: 9231 Cov.: 32 AF XY: 0.330 AC XY: 24518 AN XY: 74360

African (AFR) AF: 0.478 AC: 19816 AN: 41452

American (AMR) AF: 0.309 AC: 4727 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3061 AN: 5176

South Asian (SAS) AF: 0.358 AC: 1729 AN: 4826

European-Finnish (FIN) AF: 0.212 AC: 2247 AN: 10578

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16602 AN: 67984

Other (OTH) AF: 0.305 AC: 646 AN: 2116

Alfa AF: 0.247 Hom.: 1856

Bravo AF: 0.342

Asia WGS AF: 0.429 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.41
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs6097807; hg19: chr20-52769455;