rs6162

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000102.4(CYP17A1):c.138C>T(p.His46His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,602,888 control chromosomes in the GnomAD database, including 133,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12664 hom., cov: 32)

Exomes 𝑓: 0.41 ( 121047 hom. )

Consequence

CYP17A1
NM_000102.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.106

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:

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=-0.82).

BP6

Variant 10-102837224-G-A is Benign according to our data. Variant chr10-102837224-G-A is described in ClinVar as [Benign]. Clinvar id is 298625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102837224-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.106 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4 link	c.138C>T	p.His46His	synonymous_variant	Exon 1 of 8	ENST00000369887.4	NP_000093.1	P05093Q1HB44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4 link	c.138C>T	p.His46His	synonymous_variant	Exon 1 of 8	1	NM_000102.4	ENSP00000358903.3		P05093

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61546

AN:

151954

Hom.:

12650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.408

GnomAD3 exomes

AF:

0.423

AC:

106461

AN:

251466

Hom.:

22884

AF XY:

0.426

AC XY:

57913

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.403

Gnomad ASJ exome

AF:

0.428

Gnomad EAS exome

AF:

0.569

Gnomad SAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.406

AC:

588632

AN:

1450818

Hom.:

121047

Cov.:

AF XY:

0.409

AC XY:

295225

AN XY:

722374

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.408

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.479

Gnomad4 FIN exome

AF:

0.375

Gnomad4 NFE exome

AF:

0.398

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.405

AC:

61602

AN:

152070

Hom.:

12664

Cov.:

AF XY:

0.403

AC XY:

29977

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.373

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.439

Gnomad4 EAS

AF:

0.563

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.417

Gnomad4 OTH

AF:

0.410

Alfa

AF:

0.413

Hom.:

14342

Bravo

AF:

0.406

Asia WGS

AF:

0.469

AC:

1626

AN:

3478

EpiCase

AF:

0.407

EpiControl

AF:

0.409

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 02, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Deficiency of steroid 17-alpha-monooxygenase

Benign:3

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.3

DANN

Benign

0.68

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