rs4919686

Variant names:

• chr10-102832492-A-C
• rs4919686
• NM_000102.4:c.1139+19T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-102832492-A-C
• chr10-102832492-A-T

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.1139+19T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,550,476 control chromosomes in the GnomAD database, including 55,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4200 hom., cov: 31)
  • Exomes 𝑓: 0.26 (50870 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.55
• Publications: 38 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=-0.91).
• BP6: Variant 10-102832492-A-C is Benign according to our data. Variant chr10-102832492-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	NM_000102.4	MANE Select	c.1139+19T>G		intron	N/A	NP_000093.1	Q1HB44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	ENST00000369887.4	TSL:1 MANE Select	c.1139+19T>G		intron	N/A	ENSP00000358903.3	P05093
	CYP17A1	ENST00000960108.1		c.1166+19T>G		intron	N/A	ENSP00000630166.1
	CYP17A1	ENST00000960123.1		c.1166+19T>G		intron	N/A	ENSP00000630182.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32236 AN: 151868 Hom.: 4200 Cov.: 31

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.225

GnomAD2 exomes AF: 0.226 AC: 56453 AN: 250178 AF XY: 0.227

Gnomad AFR exome AF: 0.0649

Gnomad AMR exome AF: 0.178

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.260 AC: 362997 AN: 1398490 Hom.: 50870 Cov.: 25 AF XY: 0.257 AC XY: 179419 AN XY: 699356

African (AFR) AF: 0.0615 AC: 1998 AN: 32478

American (AMR) AF: 0.182 AC: 8134 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7339 AN: 25766

East Asian (EAS) AF: 0.101 AC: 3975 AN: 39436

South Asian (SAS) AF: 0.104 AC: 8843 AN: 85154

European-Finnish (FIN) AF: 0.274 AC: 14516 AN: 52902

Middle Eastern (MID) AF: 0.272 AC: 1476 AN: 5436

European-Non Finnish (NFE) AF: 0.287 AC: 302227 AN: 1054212

Other (OTH) AF: 0.248 AC: 14489 AN: 58456

GnomAD4 genome AF: 0.212 AC: 32231 AN: 151986 Hom.: 4200 Cov.: 31 AF XY: 0.208 AC XY: 15461 AN XY: 74300

African (AFR) AF: 0.0701 AC: 2909 AN: 41502

American (AMR) AF: 0.211 AC: 3226 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3466

East Asian (EAS) AF: 0.144 AC: 738 AN: 5134

South Asian (SAS) AF: 0.0983 AC: 473 AN: 4810

European-Finnish (FIN) AF: 0.269 AC: 2844 AN: 10578

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20280 AN: 67910

Other (OTH) AF: 0.223 AC: 470 AN: 2106

Alfa AF: 0.268 Hom.: 13041

Bravo AF: 0.203

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Deficiency of steroid 17-alpha-monooxygenase (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.032
DANN	Benign	0.39
PhyloP100		-1.5
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: rs4919686; hg19: chr10-104592249; COSMIC: COSV64004884; COSMIC: COSV64004884;