rs4919686

Positions:

chr10-102832492-A-C

Variant summary

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

The NM_000102.4(CYP17A1):c.1139+19T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,550,476 control chromosomes in the GnomAD database, including 55,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4200 hom., cov: 31)

Exomes 𝑓: 0.26 ( 50870 hom. )

Consequence

CYP17A1
NM_000102.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.55

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:

WBP1L (HGNC:23510): (WW domain binding protein 1 like) Predicted to enable ubiquitin protein ligase binding activity. Predicted to act upstream of or within CXCL12-activated CXCR4 signaling pathway; hemopoiesis; and positive regulation of protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

WBP1L links:

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=-0.91).

BP6

Variant 10-102832492-A-C is Benign according to our data. Variant chr10-102832492-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 137063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102832492-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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.1139+19T>G		intron_variant		ENST00000369887.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP17A1	ENST00000369887.4 linkuse as main transcript	c.1139+19T>G		intron_variant		1	NM_000102.4	P3

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32236

AN:

151868

Hom.:

4200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0703

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.0972

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.226

AC:

56453

AN:

250178

Hom.:

7340

AF XY:

0.227

AC XY:

30720

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.0649

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.260

AC:

362997

AN:

1398490

Hom.:

50870

Cov.:

AF XY:

0.257

AC XY:

179419

AN XY:

699356

show subpopulations

Gnomad4 AFR exome

AF:

0.0615

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.287

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.212

AC:

32231

AN:

151986

Hom.:

4200

Cov.:

AF XY:

0.208

AC XY:

15461

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0701

Gnomad4 AMR

AF:

0.211

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.0983

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.274

Hom.:

9043

Bravo

AF:

0.203

Asia WGS

AF:

0.103

AC:

359

AN:

3478

ClinVar

Significance: Benign/Likely 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	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 02, 2017	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 10, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Deficiency of steroid 17-alpha-monooxygenase

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.032

DANN

Benign

0.39

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