Variant rs1004467 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.666+35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,754 control chromosomes in the GnomAD database, including 13,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1803 hom., cov: 32)

Exomes 𝑓: 0.11 ( 11962 hom. )

Consequence

CYP17A1
NM_000102.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.231

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-102834750-A-G is Benign according to our data. Variant chr10-102834750-A-G is described in ClinVar as [Benign]. Clinvar id is 1177609.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.666+35T>C		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.666+35T>C		intron_variant		1	NM_000102.4	ENSP00000358903	P3

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21353

AN:

151986

Hom.:

1798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.0905

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.0871

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0996

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.153

AC:

38333

AN:

250872

Hom.:

3712

AF XY:

0.151

AC XY:

20474

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.0993

Gnomad EAS exome

AF:

0.341

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.0918

Gnomad NFE exome

AF:

0.0959

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.112

AC:

163288

AN:

1461650

Hom.:

11962

Cov.:

AF XY:

0.115

AC XY:

83595

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.0959

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.0908

Gnomad4 NFE exome

AF:

0.0889

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.141

AC:

21398

AN:

152104

Hom.:

1803

Cov.:

AF XY:

0.142

AC XY:

10529

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.0905

Gnomad4 EAS

AF:

0.343

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.0871

Gnomad4 NFE

AF:

0.0996

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.114

Hom.:

1815

Bravo

AF:

0.150

Asia WGS

AF:

0.247

AC:

858

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	-	- -

Deficiency of steroid 17-alpha-monooxygenase

Benign:1

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

-0.85

CADD

Benign

3.2

DANN

Benign

0.67

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