chr20-54166141-G-A

Variant names:

• chr20-54166141-G-A
• rs3787554
• NM_000782.5:c.641-308C>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.641-308C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 152,156 control chromosomes in the GnomAD database, including 625 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 0.078 (625 hom., cov: 32)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 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.641-308C>T		intron	N/A	NP_000773.2
	CYP24A1	NM_001424340.1		c.641-308C>T		intron	N/A	NP_001411269.1
	CYP24A1	NM_001424341.1		c.641-308C>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.641-308C>T		intron	N/A	ENSP00000216862.3
	CYP24A1	ENST00000395955.7	TSL:1	c.641-308C>T		intron	N/A	ENSP00000379285.3
	CYP24A1	ENST00000395954.3	TSL:1	c.215-308C>T		intron	N/A	ENSP00000379284.3

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11899 AN: 152038 Hom.: 621 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0529

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0783 AC: 11918 AN: 152156 Hom.: 625 Cov.: 32 AF XY: 0.0777 AC XY: 5779 AN XY: 74390

African (AFR) AF: 0.0307 AC: 1274 AN: 41516

American (AMR) AF: 0.0686 AC: 1049 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5180

South Asian (SAS) AF: 0.128 AC: 615 AN: 4812

European-Finnish (FIN) AF: 0.0529 AC: 560 AN: 10578

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0925 AC: 6291 AN: 67988

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.0890 Hom.: 1696

Bravo AF: 0.0769

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.33
PhyloP100		-1.4
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: rs3787554; hg19: chr20-52782680;