rs2762934

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000782.5(CYP24A1):​c.*50C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 153,476 control chromosomes in the GnomAD database, including 2,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2594 hom., cov: 29)
Exomes 𝑓: 0.21 ( 41 hom. )

Consequence

CYP24A1
NM_000782.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.100
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 20-54154722-G-A is Benign according to our data. Variant chr20-54154722-G-A is described in ClinVar as [Benign]. Clinvar id is 338810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54154722-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYP24A1NM_000782.5 linkc.*50C>T 3_prime_UTR_variant Exon 12 of 12 ENST00000216862.8 NP_000773.2 Q07973-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP24A1ENST00000216862 linkc.*50C>T 3_prime_UTR_variant Exon 12 of 12 1 NM_000782.5 ENSP00000216862.3 Q07973-1
CYP24A1ENST00000395955 linkc.*50C>T 3_prime_UTR_variant Exon 11 of 11 1 ENSP00000379285.3 Q07973-2
CYP24A1ENST00000395954 linkc.*50C>T 3_prime_UTR_variant Exon 10 of 10 1 ENSP00000379284.3 Q07973-3
CYP24A1ENST00000460643.1 linkn.342C>T non_coding_transcript_exon_variant Exon 2 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.181
AC:
27460
AN:
151716
Hom.:
2597
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.163
Gnomad AMI
AF:
0.176
Gnomad AMR
AF:
0.157
Gnomad ASJ
AF:
0.224
Gnomad EAS
AF:
0.101
Gnomad SAS
AF:
0.292
Gnomad FIN
AF:
0.232
Gnomad MID
AF:
0.244
Gnomad NFE
AF:
0.185
Gnomad OTH
AF:
0.192
GnomAD4 exome
AF:
0.215
AC:
353
AN:
1642
Hom.:
41
Cov.:
0
AF XY:
0.214
AC XY:
185
AN XY:
866
show subpopulations
Gnomad4 AFR exome
AF:
0.206
Gnomad4 AMR exome
AF:
0.114
Gnomad4 ASJ exome
AF:
0.250
Gnomad4 EAS exome
AF:
0.131
Gnomad4 SAS exome
AF:
0.500
Gnomad4 FIN exome
AF:
0.263
Gnomad4 NFE exome
AF:
0.225
Gnomad4 OTH exome
AF:
0.139
GnomAD4 genome
AF:
0.181
AC:
27471
AN:
151834
Hom.:
2594
Cov.:
29
AF XY:
0.185
AC XY:
13716
AN XY:
74176
show subpopulations
Gnomad4 AFR
AF:
0.162
Gnomad4 AMR
AF:
0.157
Gnomad4 ASJ
AF:
0.224
Gnomad4 EAS
AF:
0.101
Gnomad4 SAS
AF:
0.292
Gnomad4 FIN
AF:
0.232
Gnomad4 NFE
AF:
0.185
Gnomad4 OTH
AF:
0.196
Alfa
AF:
0.186
Hom.:
5893
Bravo
AF:
0.172
Asia WGS
AF:
0.214
AC:
745
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hypercalcemia, infantile, 1 Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
2.1
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2762934; hg19: chr20-52771261; API