10-102834750-A-G

Variant names:

• chr10-102834750-A-G
• rs1004467
• NM_000102.4:c.666+35T>C

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.231
• Publications: 128 publications found

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]

CYP17A1-AS1 (HGNC:31671): (CYP17A1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000102.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	NM_000102.4	MANE Select	c.666+35T>C		intron	N/A	NP_000093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	ENST00000369887.4	TSL:1 MANE Select	c.666+35T>C		intron	N/A	ENSP00000358903.3
	CYP17A1	ENST00000489268.1	TSL:2	n.955T>C		non_coding_transcript_exon	Exon 3 of 3
	CYP17A1	ENST00000639393.1	TSL:5	c.666+35T>C		intron	N/A	ENSP00000492651.1

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

GnomAD2 exomes AF: 0.153 AC: 38333 AN: 250872 AF XY: 0.151

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 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

African (AFR) AF: 0.191 AC: 6411 AN: 33478

American (AMR) AF: 0.210 AC: 9366 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0959 AC: 2507 AN: 26134

East Asian (EAS) AF: 0.329 AC: 13056 AN: 39698

South Asian (SAS) AF: 0.235 AC: 20266 AN: 86234

European-Finnish (FIN) AF: 0.0908 AC: 4847 AN: 53404

Middle Eastern (MID) AF: 0.103 AC: 590 AN: 5714

European-Non Finnish (NFE) AF: 0.0889 AC: 98829 AN: 1111898

Other (OTH) AF: 0.123 AC: 7416 AN: 60388

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

African (AFR) AF: 0.186 AC: 7728 AN: 41448

American (AMR) AF: 0.161 AC: 2456 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1776 AN: 5174

South Asian (SAS) AF: 0.225 AC: 1083 AN: 4820

European-Finnish (FIN) AF: 0.0871 AC: 923 AN: 10600

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0996 AC: 6775 AN: 68000

Other (OTH) AF: 0.142 AC: 300 AN: 2112

Alfa AF: 0.121 Hom.: 3397

Bravo AF: 0.150

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Deficiency of steroid 17-alpha-monooxygenase Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.67
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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