10-102835149-T-G

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.436+105A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,155,236 control chromosomes in the GnomAD database, including 42,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4840 hom., cov: 31)
  • Exomes 𝑓: 0.27 (37836 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.415

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=-0.81).
• BP6: Variant 10-102835149-T-G is Benign according to our data. Variant chr10-102835149-T-G is described in ClinVar as [Benign]. Clinvar id is 761000.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.436+105A>C		intron_variant		ENST00000369887.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP17A1	ENST00000369887.4	c.436+105A>C		intron_variant		1	NM_000102.4	P3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37164 AN: 151246 Hom.: 4839 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.267 AC: 267568 AN: 1003872 Hom.: 37836 Cov.: 14 AF XY: 0.262 AC XY: 135637 AN XY: 516718

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.246 AC: 37170 AN: 151364 Hom.: 4840 Cov.: 31 AF XY: 0.242 AC XY: 17897 AN XY: 73896

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.247

Alfa AF: 0.192 Hom.: 515

Bravo AF: 0.241

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 13, 2023	- -

Deficiency of steroid 17-alpha-monooxygenase Benign:1

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	-0.81
Cadd	Benign	2.7
Dann	Benign	0.72

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: rs743575; hg19: chr10-104594906;