rs2248137

Variant names:

• chr20-54173204-C-G
• rs2248137
• NM_000782.5:c.259-105G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-54173204-C-G
• chr20-54173204-C-A
• chr20-54173204-C-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.259-105G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,522,238 control chromosomes in the GnomAD database, including 137,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19381 hom., cov: 34)
  • Exomes 𝑓: 0.41 (118375 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.163
• Publications: 56 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-54173204-C-G is Benign according to our data. Variant chr20-54173204-C-G is described in ClinVar as Benign. ClinVar VariationId is 1241606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 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.259-105G>C		intron	N/A	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.259-105G>C		intron	N/A	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.259-105G>C		intron	N/A	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.259-105G>C		intron	N/A	ENSP00000216862.3	Q07973-1
	CYP24A1	ENST00000395955.7	TSL:1	c.259-105G>C		intron	N/A	ENSP00000379285.3	Q07973-2
	CYP24A1	ENST00000869535.1		c.259-105G>C		intron	N/A	ENSP00000539594.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73771 AN: 152102 Hom.: 19323 Cov.: 34

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.410 AC: 561659 AN: 1370018 Hom.: 118375 Cov.: 23 AF XY: 0.410 AC XY: 280736 AN XY: 684148

African (AFR) AF: 0.713 AC: 22747 AN: 31882

American (AMR) AF: 0.302 AC: 12493 AN: 41432

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 14642 AN: 25344

East Asian (EAS) AF: 0.433 AC: 16755 AN: 38668

South Asian (SAS) AF: 0.410 AC: 34106 AN: 83238

European-Finnish (FIN) AF: 0.354 AC: 16535 AN: 46686

Middle Eastern (MID) AF: 0.548 AC: 2786 AN: 5088

European-Non Finnish (NFE) AF: 0.400 AC: 416474 AN: 1040344

Other (OTH) AF: 0.438 AC: 25121 AN: 57336

GnomAD4 genome AF: 0.485 AC: 73885 AN: 152220 Hom.: 19381 Cov.: 34 AF XY: 0.481 AC XY: 35777 AN XY: 74414

African (AFR) AF: 0.702 AC: 29174 AN: 41550

American (AMR) AF: 0.381 AC: 5825 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2009 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2111 AN: 5148

South Asian (SAS) AF: 0.403 AC: 1948 AN: 4828

European-Finnish (FIN) AF: 0.371 AC: 3937 AN: 10606

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27334 AN: 67996

Other (OTH) AF: 0.485 AC: 1025 AN: 2114

Alfa AF: 0.292 Hom.: 681

Bravo AF: 0.495

Asia WGS AF: 0.422 AC: 1467 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.33
PhyloP100		-0.16
PromoterAI		-0.044	Neutral
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: rs2248137; hg19: chr20-52789743; COSMIC: COSV53776952; COSMIC: COSV53776952;