rs743572

Variant summary

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

The NM_000102(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 0.391 in 151974 control chromosomes in the gnomAD Genomes database, including 11760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11760 hom., cov: 32)

Exomes 𝑓: 0.40 ( 19776 hom. )

Consequence

CYP17A1
NM_000102 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.520

Links

CYP17A1 (HGNC:2593):

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

GnomAd 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
CYP17A1	NM_000102.4 linkuse as main transcript	c.-34T>C		5_prime_UTR_variant	1/8	ENST00000369887.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP17A1	ENST00000369887.4 linkuse as main transcript	c.-34T>C		5_prime_UTR_variant	1/8	1	NM_000102.4	P2

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59374

AN:

151974

Hom.:

11760

Cov.:

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

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

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 submitter	clinical testing	Invitae	Nov 04, 2022	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This 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 submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

1.6

Dann

Benign

0.47

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over