chr10-102831395-T-A

Variant names:

• chr10-102831395-T-A
• rs10883783
• NM_000102.4:c.1243+113A>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.1243+113A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,523,516 control chromosomes in the GnomAD database, including 58,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4855 hom., cov: 31)
  • Exomes 𝑓: 0.27 (53468 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.436
• Publications: 26 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-102831395-T-A is Benign according to our data. Variant chr10-102831395-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1177607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 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.1243+113A>T		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.1243+113A>T		intron	N/A	ENSP00000358903.3	P05093
	CYP17A1	ENST00000960108.1		c.1270+113A>T		intron	N/A	ENSP00000630166.1
	CYP17A1	ENST00000960123.1		c.1270+113A>T		intron	N/A	ENSP00000630182.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37277 AN: 151808 Hom.: 4855 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.274 AC: 375458 AN: 1371590 Hom.: 53468 AF XY: 0.270 AC XY: 183410 AN XY: 678482

African (AFR) AF: 0.158 AC: 4964 AN: 31488

American (AMR) AF: 0.197 AC: 7108 AN: 36022

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7318 AN: 25084

East Asian (EAS) AF: 0.188 AC: 6798 AN: 36152

South Asian (SAS) AF: 0.129 AC: 10234 AN: 79072

European-Finnish (FIN) AF: 0.282 AC: 10828 AN: 38388

Middle Eastern (MID) AF: 0.285 AC: 1357 AN: 4766

European-Non Finnish (NFE) AF: 0.293 AC: 311516 AN: 1063320

Other (OTH) AF: 0.268 AC: 15335 AN: 57298

GnomAD4 genome AF: 0.245 AC: 37282 AN: 151926 Hom.: 4855 Cov.: 31 AF XY: 0.242 AC XY: 17962 AN XY: 74266

African (AFR) AF: 0.165 AC: 6848 AN: 41416

American (AMR) AF: 0.230 AC: 3518 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1185 AN: 5148

South Asian (SAS) AF: 0.128 AC: 617 AN: 4818

European-Finnish (FIN) AF: 0.272 AC: 2871 AN: 10566

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20401 AN: 67922

Other (OTH) AF: 0.248 AC: 524 AN: 2116

Alfa AF: 0.278 Hom.: 760

Bravo AF: 0.240

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Deficiency of steroid 17-alpha-monooxygenase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.73
PhyloP100		0.44
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: rs10883783; hg19: chr10-104591152;