NM_000782.5:c.990+1307A>T

Variant names:

• chr20-54161410-T-A
• rs2762936
• NM_000782.5:c.990+1307A>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.990+1307A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,952 control chromosomes in the GnomAD database, including 5,907 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 0.27 (5907 hom., cov: 32)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.990+1307A>T		intron_variant	Intron 7 of 11	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.990+1307A>T		intron_variant	Intron 7 of 11	1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40517 AN: 151834 Hom.: 5904 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.267 AC: 40551 AN: 151952 Hom.: 5907 Cov.: 32 AF XY: 0.270 AC XY: 20020 AN XY: 74282

African (AFR) AF: 0.376 AC: 15586 AN: 41426

American (AMR) AF: 0.238 AC: 3639 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3468

East Asian (EAS) AF: 0.291 AC: 1503 AN: 5172

South Asian (SAS) AF: 0.406 AC: 1951 AN: 4802

European-Finnish (FIN) AF: 0.216 AC: 2276 AN: 10554

Middle Eastern (MID) AF: 0.297 AC: 86 AN: 290

European-Non Finnish (NFE) AF: 0.203 AC: 13823 AN: 67960

Other (OTH) AF: 0.281 AC: 591 AN: 2104

Alfa AF: 0.237 Hom.: 593

Bravo AF: 0.269

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.79
PhyloP100		-0.42
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: rs2762936; hg19: chr20-52777949;