20-54157940-C-T

Variant names:

• chr20-54157940-C-T
• rs1977297
• NM_000782.5:c.1236+146G>A

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.1236+146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,384,664 control chromosomes in the GnomAD database, including 12,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2933 hom., cov: 33)
  • Exomes 𝑓: 0.12 (9676 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.752
• Publications: 3 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=-0.81).
• BP6: Variant 20-54157940-C-T is Benign according to our data. Variant chr20-54157940-C-T is described in ClinVar as Benign. ClinVar VariationId is 1236993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.1236+146G>A		intron_variant	Intron 9 of 11	ENST00000216862.8	NP_000773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP24A1	ENST00000216862.8	c.1236+146G>A		intron_variant	Intron 9 of 11	1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26294 AN: 152110 Hom.: 2932 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.116 AC: 142603 AN: 1232436 Hom.: 9676 AF XY: 0.115 AC XY: 70439 AN XY: 611262

African (AFR) AF: 0.286 AC: 7933 AN: 27720

American (AMR) AF: 0.178 AC: 5794 AN: 32618

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 2091 AN: 22282

East Asian (EAS) AF: 0.309 AC: 10725 AN: 34738

South Asian (SAS) AF: 0.129 AC: 8937 AN: 69314

European-Finnish (FIN) AF: 0.114 AC: 3803 AN: 33374

Middle Eastern (MID) AF: 0.0837 AC: 310 AN: 3702

European-Non Finnish (NFE) AF: 0.101 AC: 96630 AN: 956496

Other (OTH) AF: 0.122 AC: 6380 AN: 52192

GnomAD4 genome AF: 0.173 AC: 26309 AN: 152228 Hom.: 2933 Cov.: 33 AF XY: 0.175 AC XY: 12989 AN XY: 74426

African (AFR) AF: 0.296 AC: 12270 AN: 41518

American (AMR) AF: 0.177 AC: 2712 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 344 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1571 AN: 5180

South Asian (SAS) AF: 0.132 AC: 637 AN: 4832

European-Finnish (FIN) AF: 0.110 AC: 1167 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7186 AN: 68010

Other (OTH) AF: 0.137 AC: 289 AN: 2114

Alfa AF: 0.108 Hom.: 322

Bravo AF: 0.183

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 08, 2019

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	-0.81
CADD	Benign	3.4
DANN	Benign	0.67
PhyloP100		-0.75
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: rs1977297; hg19: chr20-52774479;