rs743572

Positions:

• chr10-102837395-A-G
• chr10-102837395-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000102.4(CYP17A1):​c.-34T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,408,408 control chromosomes in the GnomAD database, including 106,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11779 hom., cov: 32)
  • Exomes 𝑓: 0.39 (94874 hom.)
• Consequence: CYP17A1 NM_000102.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.520

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-102837395-A-G is Benign according to our data. Variant chr10-102837395-A-G is described in ClinVar as [Benign]. Clinvar id is 298630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102837395-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.-34T>C		5_prime_UTR_variant	1/8	ENST00000369887.4	NP_000093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4	c.-34T>C		5_prime_UTR_variant	1/8	1	NM_000102.4	ENSP00000358903	P3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59374 AN: 151974 Hom.: 11760 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.390

GnomAD3 exomes AF: 0.398 AC: 98034 AN: 246120 Hom.: 19776 AF XY: 0.396 AC XY: 52888 AN XY: 133508

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.393

Gnomad EAS exome AF: 0.567

Gnomad SAS exome AF: 0.362

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.392

Gnomad OTH exome AF: 0.395

GnomAD4 exome AF: 0.386 AC: 484897 AN: 1256316 Hom.: 94874 Cov.: 18 AF XY: 0.386 AC XY: 245281 AN XY: 635484

Gnomad4 AFR exome AF: 0.369

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.391 AC: 59442 AN: 152092 Hom.: 11779 Cov.: 32 AF XY: 0.388 AC XY: 28875 AN XY: 74358

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.392

Alfa AF: 0.390 Hom.: 20808

Bravo AF: 0.395

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 25929975, 24629213, 7849715, 20113968, 16998812, 17307805, 19013303, 21716904, 20133979, 17606708, 9067272, 20798986) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Deficiency of steroid 17-alpha-monooxygenase Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.84
DANN	Benign	0.47

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: rs743572; hg19: chr10-104597152; COSMIC: COSV64004809; COSMIC: COSV64004809;