20-54160302-A-G

Variant names:

• chr20-54160302-A-G
• rs912505
• NM_000782.5:c.991-1179T>C

Variant summary

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

The NM_000782.5(CYP24A1):​c.991-1179T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,206 control chromosomes in the GnomAD database, including 7,275 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 0.29 (7275 hom., cov: 33)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965
• Publications: 18 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.991-1179T>C		intron_variant	Intron 7 of 11	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.991-1179T>C		intron_variant	Intron 7 of 11	1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44044 AN: 152088 Hom.: 7268 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.290 AC: 44072 AN: 152206 Hom.: 7275 Cov.: 33 AF XY: 0.292 AC XY: 21761 AN XY: 74410

African (AFR) AF: 0.412 AC: 17113 AN: 41512

American (AMR) AF: 0.273 AC: 4179 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3468

East Asian (EAS) AF: 0.606 AC: 3144 AN: 5184

South Asian (SAS) AF: 0.353 AC: 1705 AN: 4826

European-Finnish (FIN) AF: 0.204 AC: 2160 AN: 10604

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14217 AN: 67998

Other (OTH) AF: 0.266 AC: 563 AN: 2116

Alfa AF: 0.234 Hom.: 7409

Bravo AF: 0.299

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.75
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs912505; hg19: chr20-52776841;