Variant 10-102831636-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000102.4(CYP17A1):c.1140-25C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,611,846 control chromosomes in the GnomAD database, including 12,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1122 hom., cov: 31)

Exomes 𝑓: 0.11 ( 11204 hom. )

Consequence

CYP17A1
NM_000102.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.118

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=-0.86).

BP6

Variant 10-102831636-G-T is Benign according to our data. Variant chr10-102831636-G-T is described in ClinVar as [Benign]. Clinvar id is 1271411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 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.1140-25C>A		intron_variant		ENST00000369887.4	NP_000093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4 linkuse as main transcript	c.1140-25C>A		intron_variant		1	NM_000102.4	ENSP00000358903	P3

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16157

AN:

152012

Hom.:

1118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0693

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.0830

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.0870

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0990

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.143

AC:

35549

AN:

249388

Hom.:

3345

AF XY:

0.143

AC XY:

19356

AN XY:

134958

show subpopulations

Gnomad AFR exome

AF:

0.0668

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.0882

Gnomad EAS exome

AF:

0.338

Gnomad SAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.0934

Gnomad NFE exome

AF:

0.0947

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.108

AC:

157155

AN:

1459716

Hom.:

11204

Cov.:

AF XY:

0.111

AC XY:

80893

AN XY:

726198

show subpopulations

Gnomad4 AFR exome

AF:

0.0658

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.0861

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.0906

Gnomad4 NFE exome

AF:

0.0883

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.106

AC:

16176

AN:

152130

Hom.:

1122

Cov.:

AF XY:

0.109

AC XY:

8108

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0692

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.0830

Gnomad4 EAS

AF:

0.344

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.0870

Gnomad4 NFE

AF:

0.0990

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.106

Hom.:

2367

Bravo

AF:

0.110

Asia WGS

AF:

0.240

AC:

832

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.1

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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