20-54161796-G-A

Variant names:

• chr20-54161796-G-A
• rs2762938
• NM_000782.5:c.990+921C>T

Variant summary

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

The NM_000782.5(CYP24A1):​c.990+921C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,000 control chromosomes in the GnomAD database, including 28,654 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 0.61 (28654 hom., cov: 32)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 2 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 = 0.804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000782.5. 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
	CYP24A1	NM_000782.5	MANE Select	c.990+921C>T		intron	N/A	NP_000773.2
	CYP24A1	NM_001424340.1		c.990+921C>T		intron	N/A	NP_001411269.1
	CYP24A1	NM_001424341.1		c.990+921C>T		intron	N/A	NP_001411270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.990+921C>T		intron	N/A	ENSP00000216862.3
	CYP24A1	ENST00000395955.7	TSL:1	c.990+921C>T		intron	N/A	ENSP00000379285.3
	CYP24A1	ENST00000395954.3	TSL:1	c.564+921C>T		intron	N/A	ENSP00000379284.3

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92681 AN: 151880 Hom.: 28613 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.610 AC: 92779 AN: 152000 Hom.: 28654 Cov.: 32 AF XY: 0.615 AC XY: 45722 AN XY: 74290

African (AFR) AF: 0.616 AC: 25525 AN: 41406

American (AMR) AF: 0.530 AC: 8103 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2260 AN: 3470

East Asian (EAS) AF: 0.824 AC: 4271 AN: 5182

South Asian (SAS) AF: 0.781 AC: 3763 AN: 4816

European-Finnish (FIN) AF: 0.653 AC: 6895 AN: 10556

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40149 AN: 67980

Other (OTH) AF: 0.602 AC: 1268 AN: 2108

Alfa AF: 0.602 Hom.: 36128

Bravo AF: 0.595

Asia WGS AF: 0.788 AC: 2738 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	0.0030
DANN	Benign	0.71
PhyloP100		-1.8
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: rs2762938; hg19: chr20-52778335;