rs284849

chr10-102831425-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.1243+83C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,579,362 control chromosomes in the GnomAD database, including 31,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2513 hom., cov: 31)
  • Exomes 𝑓: 0.20 (28715 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.158

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=-0.87).
• BP6: Variant 10-102831425-G-T is Benign according to our data. Variant chr10-102831425-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1177608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP17A1	NM_000102.4	c.1243+83C>A		intron_variant		ENST00000369887.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP17A1	ENST00000369887.4	c.1243+83C>A		intron_variant		1	NM_000102.4	P3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24425 AN: 151968 Hom.: 2506 Cov.: 31

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.196 AC: 279263 AN: 1427276 Hom.: 28715 AF XY: 0.196 AC XY: 139026 AN XY: 707716

Gnomad4 AFR exome AF: 0.0340

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.161 AC: 24434 AN: 152086 Hom.: 2513 Cov.: 31 AF XY: 0.168 AC XY: 12461 AN XY: 74322

Gnomad4 AFR AF: 0.0424

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.157

Alfa AF: 0.175 Hom.: 390

Bravo AF: 0.151

Asia WGS AF: 0.196 AC: 680 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deficiency of steroid 17-alpha-monooxygenase Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	9.9
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs284849; hg19: chr10-104591182; COSMIC: COSV64005245; COSMIC: COSV64005245;