Variant rs4919687 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.298-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,034,328 control chromosomes in the GnomAD database, including 37,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4852 hom., cov: 32)

Exomes 𝑓: 0.26 ( 32213 hom. )

Consequence

CYP17A1
NM_000102.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.948

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 10-102835491-G-A is Benign according to our data. Variant chr10-102835491-G-A is described in ClinVar as [Benign]. Clinvar id is 1292585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 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.298-99C>T		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.298-99C>T		intron_variant		1	NM_000102.4	ENSP00000358903	P3

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37257

AN:

151984

Hom.:

4852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.262

AC:

231012

AN:

882226

Hom.:

32213

Cov.:

AF XY:

0.258

AC XY:

119719

AN XY:

463144

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.245

AC:

37262

AN:

152102

Hom.:

4852

Cov.:

AF XY:

0.242

AC XY:

17960

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.286

Hom.:

6855

Bravo

AF:

0.240

Asia WGS

AF:

0.163

AC:

566

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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