rs284849

Variant names:

• chr10-102831425-G-T
• rs284849
• NM_000102.4:c.1243+83C>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.1243+83C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,579,362 control chromosomes in the GnomAD database, including 31,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2513 hom., cov: 31)
  • Exomes 𝑓: 0.20 (28715 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.158
• Publications: 8 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=-0.87).
• BP6: Variant 10-102831425-G-T is Benign according to our data. Variant chr10-102831425-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1177608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.1243+83C>A		intron_variant	Intron 7 of 7	ENST00000369887.4	NP_000093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4	c.1243+83C>A		intron_variant	Intron 7 of 7	1	NM_000102.4	ENSP00000358903.3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24425 AN: 151968 Hom.: 2506 Cov.: 31

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.196 AC: 279263 AN: 1427276 Hom.: 28715 AF XY: 0.196 AC XY: 139026 AN XY: 707716

African (AFR) AF: 0.0340 AC: 1119 AN: 32948

American (AMR) AF: 0.290 AC: 11547 AN: 39794

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4267 AN: 25552

East Asian (EAS) AF: 0.198 AC: 7651 AN: 38650

South Asian (SAS) AF: 0.197 AC: 16320 AN: 82670

European-Finnish (FIN) AF: 0.293 AC: 13515 AN: 46170

Middle Eastern (MID) AF: 0.177 AC: 968 AN: 5484

European-Non Finnish (NFE) AF: 0.194 AC: 213149 AN: 1096722

Other (OTH) AF: 0.181 AC: 10727 AN: 59286

GnomAD4 genome AF: 0.161 AC: 24434 AN: 152086 Hom.: 2513 Cov.: 31 AF XY: 0.168 AC XY: 12461 AN XY: 74322

African (AFR) AF: 0.0424 AC: 1761 AN: 41532

American (AMR) AF: 0.235 AC: 3587 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3470

East Asian (EAS) AF: 0.148 AC: 762 AN: 5152

South Asian (SAS) AF: 0.203 AC: 980 AN: 4816

European-Finnish (FIN) AF: 0.308 AC: 3258 AN: 10568

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.191 AC: 12996 AN: 67962

Other (OTH) AF: 0.157 AC: 333 AN: 2116

Alfa AF: 0.175 Hom.: 390

Bravo AF: 0.151

Asia WGS AF: 0.196 AC: 680 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.9
DANN	Benign	0.86
PhyloP100		-0.16
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: rs284849; hg19: chr10-104591182; COSMIC: COSV64005245; COSMIC: COSV64005245;