rs6163

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000102.4(CYP17A1):c.195G>T(p.Ser65Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,589,132 control chromosomes in the GnomAD database, including 117,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11751 hom., cov: 31)

Exomes 𝑓: 0.38 ( 106210 hom. )

Consequence

CYP17A1
NM_000102.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0410

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]

CYP17A1 links:

CYP17A1 (HGNC:):

CYP17A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 10-102837167-C-A is Benign according to our data. Variant chr10-102837167-C-A is described in ClinVar as [Benign]. Clinvar id is 298624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102837167-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.041 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP17A1	NM_000102.4 linkuse as main transcript	c.195G>T	p.Ser65Ser	synonymous_variant	1/8	ENST00000369887.4	NP_000093.1	P05093Q1HB44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4 linkuse as main transcript	c.195G>T	p.Ser65Ser	synonymous_variant	1/8	1	NM_000102.4	ENSP00000358903.3		P05093

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59297

AN:

151854

Hom.:

11733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.562

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.390

GnomAD3 exomes

AF:

0.397

AC:

99954

AN:

251462

Hom.:

20262

AF XY:

0.395

AC XY:

53713

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.567

Gnomad SAS exome

AF:

0.359

Gnomad FIN exome

AF:

0.365

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.382

AC:

548921

AN:

1437162

Hom.:

106210

Cov.:

AF XY:

0.382

AC XY:

273833

AN XY:

716492

show subpopulations

Gnomad4 AFR exome

AF:

0.366

Gnomad4 AMR exome

AF:

0.401

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.507

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.368

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.389

GnomAD4 genome

AF:

0.391

AC:

59361

AN:

151970

Hom.:

11751

Cov.:

AF XY:

0.388

AC XY:

28836

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.370

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.399

Gnomad4 EAS

AF:

0.562

Gnomad4 SAS

AF:

0.352

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.390

Hom.:

27772

Bravo

AF:

0.394

EpiCase

AF:

0.387

EpiControl

AF:

0.390

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Deficiency of steroid 17-alpha-monooxygenase

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.1

DANN

Benign

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over