20-54148933-C-T

Variant names:

• chr20-54148933-C-T
• rs4809956
• ENST00000792273.1:n.155-19505C>T

Variant summary

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

The ENST00000792273.1(ENSG00000286587):​n.155-19505C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,004 control chromosomes in the GnomAD database, including 9,308 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 0.31 (9308 hom., cov: 32)
• Consequence: ENSG00000286587 ENST00000792273.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 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.155-19505C>T		intron	N/A
	ENSG00000286587	ENST00000792274.1		n.145-19505C>T		intron	N/A
	ENSG00000286587	ENST00000792275.1		n.187-15681C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47204 AN: 151888 Hom.: 9292 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.311 AC: 47255 AN: 152004 Hom.: 9308 Cov.: 32 AF XY: 0.310 AC XY: 22995 AN XY: 74292

African (AFR) AF: 0.535 AC: 22184 AN: 41436

American (AMR) AF: 0.271 AC: 4146 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3466

East Asian (EAS) AF: 0.586 AC: 3025 AN: 5160

South Asian (SAS) AF: 0.242 AC: 1163 AN: 4814

European-Finnish (FIN) AF: 0.184 AC: 1943 AN: 10560

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13190 AN: 67970

Other (OTH) AF: 0.284 AC: 601 AN: 2114

Alfa AF: 0.266 Hom.: 1723

Bravo AF: 0.329

Asia WGS AF: 0.400 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.43
DANN	Benign	0.64
PhyloP100		-0.90

Splicing

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

Other links and lift over

dbSNP: rs4809956; hg19: chr20-52765472;