20-54157888-A-G

Variant names:

• chr20-54157888-A-G
• rs1570669
• NM_000782.5:c.1236+198T>C

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+198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,098 control chromosomes in the GnomAD database, including 14,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (14391 hom., cov: 33)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.304
• Publications: 64 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=-0.84).
• BP6: Variant 20-54157888-A-G is Benign according to our data. Variant chr20-54157888-A-G is described in ClinVar as Benign. ClinVar VariationId is 1277733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	NM_000782.5	c.1236+198T>C		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+198T>C		intron_variant	Intron 9 of 11	1	NM_000782.5	ENSP00000216862.3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63653 AN: 151980 Hom.: 14355 Cov.: 33

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.419 AC: 63738 AN: 152098 Hom.: 14391 Cov.: 33 AF XY: 0.420 AC XY: 31200 AN XY: 74350

African (AFR) AF: 0.581 AC: 24085 AN: 41472

American (AMR) AF: 0.355 AC: 5431 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1164 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3145 AN: 5166

South Asian (SAS) AF: 0.385 AC: 1858 AN: 4820

European-Finnish (FIN) AF: 0.357 AC: 3778 AN: 10574

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23205 AN: 67982

Other (OTH) AF: 0.374 AC: 791 AN: 2114

Alfa AF: 0.371 Hom.: 34071

Bravo AF: 0.424

Asia WGS AF: 0.477 AC: 1659 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 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	-0.84
CADD	Benign	2.8
DANN	Benign	0.18
PhyloP100		-0.30
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: rs1570669; hg19: chr20-52774427;