NM_000782.5:c.990+174G>A

Variant names:

• chr20-54162543-C-T
• rs6127119
• NM_000782.5:c.990+174G>A

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.990+174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 593,070 control chromosomes in the GnomAD database, including 20,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4804 hom., cov: 25)
  • Exomes 𝑓: 0.24 (15625 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-54162543-C-T is Benign according to our data. Variant chr20-54162543-C-T is described in ClinVar as Benign. ClinVar VariationId is 1282351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 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.990+174G>A		intron	N/A	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.990+174G>A		intron	N/A	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.990+174G>A		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.990+174G>A		intron	N/A	ENSP00000216862.3	Q07973-1
	CYP24A1	ENST00000395955.7	TSL:1	c.990+174G>A		intron	N/A	ENSP00000379285.3	Q07973-2
	CYP24A1	ENST00000395954.3	TSL:1	c.564+174G>A		intron	N/A	ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 34232 AN: 139646 Hom.: 4795 Cov.: 25

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.244 AC: 110636 AN: 453310 Hom.: 15625 Cov.: 4 AF XY: 0.246 AC XY: 59541 AN XY: 241660

African (AFR) AF: 0.272 AC: 3530 AN: 12992

American (AMR) AF: 0.239 AC: 6279 AN: 26266

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 3450 AN: 14494

East Asian (EAS) AF: 0.427 AC: 11804 AN: 27632

South Asian (SAS) AF: 0.293 AC: 14579 AN: 49744

European-Finnish (FIN) AF: 0.191 AC: 5530 AN: 29022

Middle Eastern (MID) AF: 0.244 AC: 569 AN: 2328

European-Non Finnish (NFE) AF: 0.222 AC: 58820 AN: 265284

Other (OTH) AF: 0.238 AC: 6075 AN: 25548

GnomAD4 genome AF: 0.245 AC: 34280 AN: 139760 Hom.: 4804 Cov.: 25 AF XY: 0.245 AC XY: 16566 AN XY: 67590

African (AFR) AF: 0.274 AC: 10224 AN: 37246

American (AMR) AF: 0.243 AC: 3372 AN: 13856

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 774 AN: 3296

East Asian (EAS) AF: 0.401 AC: 1858 AN: 4628

South Asian (SAS) AF: 0.315 AC: 1315 AN: 4178

European-Finnish (FIN) AF: 0.175 AC: 1651 AN: 9440

Middle Eastern (MID) AF: 0.230 AC: 65 AN: 282

European-Non Finnish (NFE) AF: 0.223 AC: 14258 AN: 64078

Other (OTH) AF: 0.240 AC: 458 AN: 1906

Alfa AF: 0.241 Hom.: 3475

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	-0.86
CADD	Benign	2.7
DANN	Benign	0.71
PhyloP100		-0.28
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: rs6127119; hg19: chr20-52779082;