rs1004467

chr10-102834750-A-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.666+35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,754 control chromosomes in the GnomAD database, including 13,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1803 hom., cov: 32)
  • Exomes 𝑓: 0.11 (11962 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.231

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=-0.85).
• BP6: Variant 10-102834750-A-G is Benign according to our data. Variant chr10-102834750-A-G is described in ClinVar as [Benign]. Clinvar id is 1177609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.666+35T>C		intron_variant		ENST00000369887.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP17A1	ENST00000369887.4	c.666+35T>C		intron_variant		1	NM_000102.4	P3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21353 AN: 151986 Hom.: 1798 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.139

GnomAD3 exomes AF: 0.153 AC: 38333 AN: 250872 Hom.: 3712 AF XY: 0.151 AC XY: 20474 AN XY: 135640

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.0993

Gnomad EAS exome AF: 0.341

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.0918

Gnomad NFE exome AF: 0.0959

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.112 AC: 163288 AN: 1461650 Hom.: 11962 Cov.: 32 AF XY: 0.115 AC XY: 83595 AN XY: 727124

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.0959

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.0908

Gnomad4 NFE exome AF: 0.0889

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.141 AC: 21398 AN: 152104 Hom.: 1803 Cov.: 32 AF XY: 0.142 AC XY: 10529 AN XY: 74346

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.0871

Gnomad4 NFE AF: 0.0996

Gnomad4 OTH AF: 0.142

Alfa AF: 0.114 Hom.: 1815

Bravo AF: 0.150

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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	-0.85
Cadd	Benign	3.2
Dann	Benign	0.67

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: rs1004467; hg19: chr10-104594507; COSMIC: COSV64004950; COSMIC: COSV64004950;