rs11907350

Variant names:

• chr20-54153900-G-A
• rs11907350
• NM_000782.5:c.*872C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000782.5(CYP24A1):​c.*872C>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 0.0666 in 152,480 control chromosomes in the GnomAD database, including 705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (705 hom., cov: 33)
  • Exomes 𝑓: 0.032 (0 hom.)
• Consequence: CYP24A1 NM_000782.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-54153900-G-A is Benign according to our data. Variant chr20-54153900-G-A is described in ClinVar as Benign. ClinVar VariationId is 338794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.*872C>T		3_prime_UTR	Exon 12 of 12	NP_000773.2
	CYP24A1	NM_001424340.1		c.*892C>T		3_prime_UTR	Exon 12 of 12	NP_001411269.1
	CYP24A1	NM_001424341.1		c.*1044C>T		3_prime_UTR	Exon 12 of 12	NP_001411270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.*872C>T		3_prime_UTR	Exon 12 of 12	ENSP00000216862.3
	ENSG00000286587	ENST00000792273.1		n.155-14538G>A		intron	N/A
	ENSG00000286587	ENST00000792274.1		n.145-14538G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10138 AN: 152016 Hom.: 706 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0321

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.0642

GnomAD4 exome AF: 0.0318 AC: 11 AN: 346 Hom.: 0 Cov.: 0 AF XY: 0.0340 AC XY: 7 AN XY: 206

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0324 AC: 11 AN: 340

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0667 AC: 10145 AN: 152134 Hom.: 705 Cov.: 33 AF XY: 0.0659 AC XY: 4899 AN XY: 74366

African (AFR) AF: 0.171 AC: 7110 AN: 41488

American (AMR) AF: 0.0354 AC: 541 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4818

European-Finnish (FIN) AF: 0.0381 AC: 403 AN: 10580

Middle Eastern (MID) AF: 0.0276 AC: 8 AN: 290

European-Non Finnish (NFE) AF: 0.0249 AC: 1696 AN: 68004

Other (OTH) AF: 0.0636 AC: 134 AN: 2108

Alfa AF: 0.0430 Hom.: 429

Bravo AF: 0.0709

Asia WGS AF: 0.0130 AC: 46 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hypercalcemia, infantile, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.55
PhyloP100		-1.3
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: rs11907350; hg19: chr20-52770439;