rs2762934

Variant names:

• chr20-54154722-G-A
• rs2762934
• NM_000782.5:c.*50C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000782.5(CYP24A1):​c.*50C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 153,476 control chromosomes in the GnomAD database, including 2,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2594 hom., cov: 29)
  • Exomes 𝑓: 0.21 (41 hom.)
• Consequence: CYP24A1 NM_000782.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.100
• Publications: 50 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, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• autosomal recessive infantile hypercalcemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-54154722-G-A is Benign according to our data. Variant chr20-54154722-G-A is described in ClinVar as Benign. ClinVar VariationId is 338810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	NM_000782.5	MANE Select	c.*50C>T		3_prime_UTR	Exon 12 of 12	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.*70C>T		3_prime_UTR	Exon 12 of 12	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.*222C>T		3_prime_UTR	Exon 12 of 12	NP_001411270.1	Q07973-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.*50C>T		3_prime_UTR	Exon 12 of 12	ENSP00000216862.3	Q07973-1
	CYP24A1	ENST00000395955.7	TSL:1	c.*50C>T		3_prime_UTR	Exon 11 of 11	ENSP00000379285.3	Q07973-2
	CYP24A1	ENST00000395954.3	TSL:1	c.*50C>T		3_prime_UTR	Exon 10 of 10	ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27460 AN: 151716 Hom.: 2597 Cov.: 29

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.215 AC: 353 AN: 1642 Hom.: 41 Cov.: 0 AF XY: 0.214 AC XY: 185 AN XY: 866

African (AFR) AF: 0.206 AC: 7 AN: 34

American (AMR) AF: 0.114 AC: 5 AN: 44

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 14 AN: 56

East Asian (EAS) AF: 0.131 AC: 26 AN: 198

South Asian (SAS) AF: 0.500 AC: 6 AN: 12

European-Finnish (FIN) AF: 0.263 AC: 59 AN: 224

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.225 AC: 225 AN: 1000

Other (OTH) AF: 0.139 AC: 10 AN: 72

GnomAD4 genome AF: 0.181 AC: 27471 AN: 151834 Hom.: 2594 Cov.: 29 AF XY: 0.185 AC XY: 13716 AN XY: 74176

African (AFR) AF: 0.162 AC: 6728 AN: 41420

American (AMR) AF: 0.157 AC: 2393 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 777 AN: 3464

East Asian (EAS) AF: 0.101 AC: 522 AN: 5168

South Asian (SAS) AF: 0.292 AC: 1403 AN: 4804

European-Finnish (FIN) AF: 0.232 AC: 2436 AN: 10492

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12572 AN: 67948

Other (OTH) AF: 0.196 AC: 412 AN: 2098

Alfa AF: 0.183 Hom.: 9292

Bravo AF: 0.172

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hypercalcemia, infantile, 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.71
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2762934; hg19: chr20-52771261;