rs4919687

Variant names:

• chr10-102835491-G-A
• rs4919687
• NM_000102.4:c.298-99C>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.298-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,034,328 control chromosomes in the GnomAD database, including 37,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4852 hom., cov: 32)
  • Exomes 𝑓: 0.26 (32213 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.948
• Publications: 52 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: Orphanet, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-102835491-G-A is Benign according to our data. Variant chr10-102835491-G-A is described in ClinVar as Benign. ClinVar VariationId is 1292585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.298-99C>T		intron_variant	Intron 1 of 7	ENST00000369887.4	NP_000093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4	c.298-99C>T		intron_variant	Intron 1 of 7	1	NM_000102.4	ENSP00000358903.3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37257 AN: 151984 Hom.: 4852 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.262 AC: 231012 AN: 882226 Hom.: 32213 Cov.: 12 AF XY: 0.258 AC XY: 119719 AN XY: 463144

African (AFR) AF: 0.160 AC: 3608 AN: 22530

American (AMR) AF: 0.191 AC: 8399 AN: 43864

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 6580 AN: 22578

East Asian (EAS) AF: 0.181 AC: 6706 AN: 37096

South Asian (SAS) AF: 0.129 AC: 9599 AN: 74168

European-Finnish (FIN) AF: 0.278 AC: 13819 AN: 49768

Middle Eastern (MID) AF: 0.287 AC: 1338 AN: 4660

European-Non Finnish (NFE) AF: 0.290 AC: 169958 AN: 586060

Other (OTH) AF: 0.265 AC: 11005 AN: 41502

GnomAD4 genome AF: 0.245 AC: 37262 AN: 152102 Hom.: 4852 Cov.: 32 AF XY: 0.242 AC XY: 17960 AN XY: 74346

African (AFR) AF: 0.166 AC: 6895 AN: 41508

American (AMR) AF: 0.232 AC: 3536 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1070 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1198 AN: 5172

South Asian (SAS) AF: 0.128 AC: 616 AN: 4824

European-Finnish (FIN) AF: 0.267 AC: 2823 AN: 10580

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

European-Non Finnish (NFE) AF: 0.300 AC: 20361 AN: 67962

Other (OTH) AF: 0.246 AC: 518 AN: 2108

Alfa AF: 0.283 Hom.: 9911

Bravo AF: 0.240

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.59
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4919687; hg19: chr10-104595248; COSMIC: COSV64004688; COSMIC: COSV64004688;