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rs743572

Variant summary

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

The NM_000102.4(CYP17A1):c.-34T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,408,408 control chromosomes in the GnomAD database, including 106,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11779 hom., cov: 32)
Exomes 𝑓: 0.39 ( 94874 hom. )

Consequence

CYP17A1
NM_000102.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.520
Variant links:
Genes affected
CYP17A1 (HGNC:2593): (cytochrome P450 family 17 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 protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia. [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=-0.83).
BP6
Variant 10-102837395-A-G is Benign according to our data. Variant chr10-102837395-A-G is described in ClinVar as [Benign]. Clinvar id is 298630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102837395-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP17A1NM_000102.4 linkuse as main transcriptc.-34T>C 5_prime_UTR_variant 1/8 ENST00000369887.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP17A1ENST00000369887.4 linkuse as main transcriptc.-34T>C 5_prime_UTR_variant 1/81 NM_000102.4 P3

Frequencies

GnomAD3 genomes
AF:
0.391
AC:
59374
AN:
151974
Hom.:
11760
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.370
Gnomad AMI
AF:
0.198
Gnomad AMR
AF:
0.396
Gnomad ASJ
AF:
0.399
Gnomad EAS
AF:
0.561
Gnomad SAS
AF:
0.352
Gnomad FIN
AF:
0.354
Gnomad MID
AF:
0.370
Gnomad NFE
AF:
0.400
Gnomad OTH
AF:
0.390
GnomAD3 exomes
AF:
0.398
AC:
98034
AN:
246120
Hom.:
19776
AF XY:
0.396
AC XY:
52888
AN XY:
133508
show subpopulations
Gnomad AFR exome
AF:
0.368
Gnomad AMR exome
AF:
0.398
Gnomad ASJ exome
AF:
0.393
Gnomad EAS exome
AF:
0.567
Gnomad SAS exome
AF:
0.362
Gnomad FIN exome
AF:
0.364
Gnomad NFE exome
AF:
0.392
Gnomad OTH exome
AF:
0.395
GnomAD4 exome
AF:
0.386
AC:
484897
AN:
1256316
Hom.:
94874
Cov.:
18
AF XY:
0.386
AC XY:
245281
AN XY:
635484
show subpopulations
Gnomad4 AFR exome
AF:
0.369
Gnomad4 AMR exome
AF:
0.403
Gnomad4 ASJ exome
AF:
0.388
Gnomad4 EAS exome
AF:
0.506
Gnomad4 SAS exome
AF:
0.367
Gnomad4 FIN exome
AF:
0.367
Gnomad4 NFE exome
AF:
0.383
Gnomad4 OTH exome
AF:
0.391
GnomAD4 genome
AF:
0.391
AC:
59442
AN:
152092
Hom.:
11779
Cov.:
32
AF XY:
0.388
AC XY:
28875
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.370
Gnomad4 AMR
AF:
0.395
Gnomad4 ASJ
AF:
0.399
Gnomad4 EAS
AF:
0.561
Gnomad4 SAS
AF:
0.354
Gnomad4 FIN
AF:
0.354
Gnomad4 NFE
AF:
0.400
Gnomad4 OTH
AF:
0.392
Alfa
AF:
0.390
Hom.:
20808
Bravo
AF:
0.395

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 22, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015This variant is associated with the following publications: (PMID: 25929975, 24629213, 7849715, 20113968, 16998812, 17307805, 19013303, 21716904, 20133979, 17606708, 9067272, 20798986) -
Deficiency of steroid 17-alpha-monooxygenase Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 2018This 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. -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 01, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
0.84
Dann
Benign
0.47

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs743572; hg19: chr10-104597152; COSMIC: COSV64004809; COSMIC: COSV64004809; API