Variant 10-102830536-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000102.4(CYP17A1):c.*165_*166insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 357,468 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0051 ( 2 hom., cov: 32)

Exomes 𝑓: 0.21 ( 0 hom. )

Consequence

CYP17A1
NM_000102.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0520

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 -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 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.165_166insT		3_prime_UTR_variant	8/8	ENST00000369887.4	NP_000093.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
CYP17A1	ENST00000369887.4 linkuse as main transcript	c.165_166insT	3_prime_UTR_variant	8/8	1	NM_000102.4	ENSP00000358903	P3
CYP17A1	ENST00000638190.1 linkuse as main transcript	c.165_166insT	3_prime_UTR_variant	6/6	5		ENSP00000492539
CYP17A1	ENST00000638971.1 linkuse as main transcript	c.165_166insT	3_prime_UTR_variant	7/7	5		ENSP00000492313
WBP1L	ENST00000647664.1 linkuse as main transcript	c.*418-189dup	intron_variant, NMD_transcript_variant				ENSP00000498131

Frequencies

GnomAD3 genomes

AF:

0.00510

AC:

743

AN:

145816

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00246

Gnomad ASJ

AF:

0.000295

Gnomad EAS

AF:

0.00179

Gnomad SAS

AF:

0.00260

Gnomad FIN

AF:

0.00277

Gnomad MID

AF:

0.00654

Gnomad NFE

AF:

0.000606

Gnomad OTH

AF:

0.00500

GnomAD4 exome

AF:

0.213

AC:

45081

AN:

211584

Hom.:

Cov.:

AF XY:

0.212

AC XY:

23746

AN XY:

111948

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.221

Gnomad4 FIN exome

AF:

0.189

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.00513

AC:

749

AN:

145884

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

344

AN XY:

70766

show subpopulations

Gnomad4 AFR

AF:

0.0153

Gnomad4 AMR

AF:

0.00246

Gnomad4 ASJ

AF:

0.000295

Gnomad4 EAS

AF:

0.00179

Gnomad4 SAS

AF:

0.00260

Gnomad4 FIN

AF:

0.00277

Gnomad4 NFE

AF:

0.000606

Gnomad4 OTH

AF:

0.00495

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital adrenal hyperplasia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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