20-54171775-T-C

Variant names:

• chr20-54171775-T-C
• rs2259735
• ENST00000395954.3:c.-82A>G

Variant summary

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

The ENST00000395954.3(CYP24A1):​c.-82A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,598,548 control chromosomes in the GnomAD database, including 165,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (22248 hom., cov: 32)
  • Exomes 𝑓: 0.44 (143355 hom.)
• Consequence: CYP24A1 ENST00000395954.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.83
• Publications: 20 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=-0.88).
• BP6: Variant 20-54171775-T-C is Benign according to our data. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54171775-T-C is described in CliVar as Benign. Clinvar id is 1291952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.450-105A>G		intron_variant	Intron 2 of 11	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.450-105A>G		intron_variant	Intron 2 of 11	1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78961 AN: 151766 Hom.: 22187 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.438 AC: 633090 AN: 1446664 Hom.: 143355 Cov.: 31 AF XY: 0.439 AC XY: 315466 AN XY: 719060

African (AFR) AF: 0.761 AC: 25189 AN: 33090

American (AMR) AF: 0.371 AC: 15913 AN: 42842

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 15925 AN: 25798

East Asian (EAS) AF: 0.706 AC: 27865 AN: 39480

South Asian (SAS) AF: 0.469 AC: 39920 AN: 85140

European-Finnish (FIN) AF: 0.359 AC: 17501 AN: 48750

Middle Eastern (MID) AF: 0.563 AC: 3235 AN: 5746

European-Non Finnish (NFE) AF: 0.415 AC: 459112 AN: 1105886

Other (OTH) AF: 0.474 AC: 28430 AN: 59932

GnomAD4 genome AF: 0.521 AC: 79081 AN: 151884 Hom.: 22248 Cov.: 32 AF XY: 0.517 AC XY: 38414 AN XY: 74238

African (AFR) AF: 0.745 AC: 30853 AN: 41388

American (AMR) AF: 0.418 AC: 6393 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2139 AN: 3466

East Asian (EAS) AF: 0.674 AC: 3483 AN: 5166

South Asian (SAS) AF: 0.470 AC: 2256 AN: 4796

European-Finnish (FIN) AF: 0.387 AC: 4077 AN: 10548

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28254 AN: 67922

Other (OTH) AF: 0.519 AC: 1098 AN: 2114

Alfa AF: 0.454 Hom.: 2058

Bravo AF: 0.534

Asia WGS AF: 0.563 AC: 1956 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.048
DANN	Benign	0.32
PhyloP100		-1.8
PromoterAI		-0.021	Neutral
Mutation Taster		=300/0	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: rs2259735; hg19: chr20-52788314; COSMIC: COSV53772921; COSMIC: COSV53772921;