10-102831636-G-T

Variant names:

• chr10-102831636-G-T
• rs17115100
• NM_000102.4:c.1140-25C>A

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.1140-25C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,611,846 control chromosomes in the GnomAD database, including 12,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1122 hom., cov: 31)
  • Exomes 𝑓: 0.11 (11204 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.118
• Publications: 73 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=-0.86).
• BP6: Variant 10-102831636-G-T is Benign according to our data. Variant chr10-102831636-G-T is described in ClinVar as Benign. ClinVar VariationId is 1271411.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.1140-25C>A		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.1140-25C>A		intron	N/A	ENSP00000358903.3
	CYP17A1	ENST00000469683.1	TSL:2	n.68C>A		non_coding_transcript_exon	Exon 1 of 2
	WBP1L	ENST00000647664.1		n.*667G>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000498131.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16157 AN: 152012 Hom.: 1118 Cov.: 31

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0830

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.0870

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0990

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.143 AC: 35549 AN: 249388 AF XY: 0.143

Gnomad AFR exome AF: 0.0668

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.0882

Gnomad EAS exome AF: 0.338

Gnomad FIN exome AF: 0.0934

Gnomad NFE exome AF: 0.0947

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.108 AC: 157155 AN: 1459716 Hom.: 11204 Cov.: 33 AF XY: 0.111 AC XY: 80893 AN XY: 726198

African (AFR) AF: 0.0658 AC: 2203 AN: 33480

American (AMR) AF: 0.200 AC: 8931 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0861 AC: 2249 AN: 26132

East Asian (EAS) AF: 0.334 AC: 13241 AN: 39678

South Asian (SAS) AF: 0.234 AC: 20202 AN: 86212

European-Finnish (FIN) AF: 0.0906 AC: 4669 AN: 51544

Middle Eastern (MID) AF: 0.0924 AC: 533 AN: 5768

European-Non Finnish (NFE) AF: 0.0883 AC: 98185 AN: 1111862

Other (OTH) AF: 0.115 AC: 6942 AN: 60370

GnomAD4 genome AF: 0.106 AC: 16176 AN: 152130 Hom.: 1122 Cov.: 31 AF XY: 0.109 AC XY: 8108 AN XY: 74350

African (AFR) AF: 0.0692 AC: 2874 AN: 41508

American (AMR) AF: 0.146 AC: 2231 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 288 AN: 3468

East Asian (EAS) AF: 0.344 AC: 1771 AN: 5152

South Asian (SAS) AF: 0.223 AC: 1071 AN: 4808

European-Finnish (FIN) AF: 0.0870 AC: 922 AN: 10600

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0990 AC: 6731 AN: 67998

Other (OTH) AF: 0.119 AC: 251 AN: 2114

Alfa AF: 0.106 Hom.: 3563

Bravo AF: 0.110

Asia WGS AF: 0.240 AC: 832 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

GeneDx

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	-0.86
CADD	Benign	3.1
DANN	Benign	0.66
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17115100; hg19: chr10-104591393; COSMIC: COSV64005097; COSMIC: COSV64005097;