rs2486758

Variant names:

• chr10-102837723-T-C
• rs2486758
• ENST00000960106.1:c.-362A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-102837723-T-C
• chr10-102837723-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000960106.1(CYP17A1):​c.-362A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,064 control chromosomes in the GnomAD database, including 3,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3114 hom., cov: 31)
• Consequence: CYP17A1 ENST00000960106.1 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.855
• Publications: 43 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]

CYP17A1 Gene-Disease associations (from GenCC):

• congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• 46,XY disorder of sex development due to isolated 17,20-lyase deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-102837723-T-C is Benign according to our data. Variant chr10-102837723-T-C is described in ClinVar as Benign. ClinVar VariationId is 1247676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000960106.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	ENST00000960106.1		c.-362A>G		upstream_gene	N/A	ENSP00000630165.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27970 AN: 151948 Hom.: 3107 Cov.: 31

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.184 AC: 27983 AN: 152064 Hom.: 3114 Cov.: 31 AF XY: 0.193 AC XY: 14345 AN XY: 74318

African (AFR) AF: 0.0681 AC: 2824 AN: 41490

American (AMR) AF: 0.256 AC: 3913 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 574 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1061 AN: 5168

South Asian (SAS) AF: 0.258 AC: 1244 AN: 4826

European-Finnish (FIN) AF: 0.340 AC: 3585 AN: 10544

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14171 AN: 67984

Other (OTH) AF: 0.189 AC: 398 AN: 2110

Alfa AF: 0.200 Hom.: 6043

Bravo AF: 0.174

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.8
DANN	Benign	0.87
PhyloP100		-0.85
PromoterAI		-0.12	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2486758; hg19: chr10-104597480;