rs4919687

chr10-102835491-G-A

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.298-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,034,328 control chromosomes in the GnomAD database, including 37,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4852 hom., cov: 32)
  • Exomes 𝑓: 0.26 (32213 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.948

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=-0.59).
• BP6: Variant 10-102835491-G-A is Benign according to our data. Variant chr10-102835491-G-A is described in ClinVar as [Benign]. Clinvar id is 1292585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP17A1	NM_000102.4	c.298-99C>T		intron_variant		ENST00000369887.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP17A1	ENST00000369887.4	c.298-99C>T		intron_variant		1	NM_000102.4	P3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37257 AN: 151984 Hom.: 4852 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.262 AC: 231012 AN: 882226 Hom.: 32213 Cov.: 12 AF XY: 0.258 AC XY: 119719 AN XY: 463144

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.245 AC: 37262 AN: 152102 Hom.: 4852 Cov.: 32 AF XY: 0.242 AC XY: 17960 AN XY: 74346

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.246

Alfa AF: 0.286 Hom.: 6855

Bravo AF: 0.240

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	11
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4919687; hg19: chr10-104595248; COSMIC: COSV64004688; COSMIC: COSV64004688;