chr10-102837224-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

51 publications found

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 Gene-Disease associations (from GenCC):

congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
46,XY disorder of sex development due to isolated 17,20-lyase deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CYP17A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 298625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.423

AC:

106461

AN:

251466

AF XY:

0.426

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 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

African (AFR)

AF:

0.370

AC:

12313

AN:

33264

American (AMR)

AF:

0.408

AC:

18255

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

11012

AN:

26080

East Asian (EAS)

AF:

0.508

AC:

20130

AN:

39632

South Asian (SAS)

AF:

0.479

AC:

41213

AN:

86054

European-Finnish (FIN)

AF:

0.375

AC:

20016

AN:

53416

Middle Eastern (MID)

AF:

0.442

AC:

2540

AN:

5752

European-Non Finnish (NFE)

AF:

0.398

AC:

438225

AN:

1101846

Other (OTH)

AF:

0.415

AC:

24928

AN:

60052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

17177

34354

51531

68708

85885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13512

27024

40536

54048

67560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.405

AC:

61602

AN:

152070

Hom.:

12664

Cov.:

AF XY:

0.403

AC XY:

29977

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.373

AC:

15492

AN:

41488

American (AMR)

AF:

0.403

AC:

6164

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1525

AN:

3470

East Asian (EAS)

AF:

0.563

AC:

2904

AN:

5154

South Asian (SAS)

AF:

0.467

AC:

2251

AN:

4822

European-Finnish (FIN)

AF:

0.358

AC:

3790

AN:

10574

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.417

AC:

28304

AN:

67952

Other (OTH)

AF:

0.410

AC:

868

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1892

3784

5675

7567

9459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.414

Hom.:

19572

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

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

- -

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

- -

Deficiency of steroid 17-alpha-monooxygenase

Benign:3

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. -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.3

(source)

DANN

Benign

0.68

PhyloP100

-0.11

PromoterAI

-0.0084

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over