rs17115100

chr10-102831636-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.118

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
CYP17A1	NM_000102.4	c.1140-25C>A		intron_variant		ENST00000369887.4

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16157 AN: 152012 Hom.: 1118 Cov.: 31

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

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.: 33 AF XY: 0.111 AC XY: 80893 AN XY: 726198

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.: 31 AF XY: 0.109 AC XY: 8108 AN XY: 74350

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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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

Other links and lift over

dbSNP: rs17115100; hg19: chr10-104591393; COSMIC: COSV64005097; COSMIC: COSV64005097;