10-102836092-G-C

Variant names:

• chr10-102836092-G-C
• rs3824755
• NM_000102.4:c.298-700C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000102.4(CYP17A1):​c.298-700C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,156 control chromosomes in the GnomAD database, including 1,821 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1821 hom., cov: 31)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 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.298-700C>G		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.298-700C>G		intron	N/A	ENSP00000358903.3	P05093
	CYP17A1	ENST00000960108.1		c.298-700C>G		intron	N/A	ENSP00000630166.1
	CYP17A1	ENST00000960123.1		c.298-700C>G		intron	N/A	ENSP00000630182.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21430 AN: 152038 Hom.: 1814 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0903

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0875

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.141 AC: 21475 AN: 152156 Hom.: 1821 Cov.: 31 AF XY: 0.143 AC XY: 10605 AN XY: 74404

African (AFR) AF: 0.190 AC: 7894 AN: 41514

American (AMR) AF: 0.159 AC: 2436 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0903 AC: 313 AN: 3466

East Asian (EAS) AF: 0.332 AC: 1718 AN: 5168

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4818

European-Finnish (FIN) AF: 0.0875 AC: 927 AN: 10590

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6768 AN: 68008

Other (OTH) AF: 0.141 AC: 298 AN: 2110

Alfa AF: 0.0493 Hom.: 45

Bravo AF: 0.150

Asia WGS AF: 0.242 AC: 837 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.62
PhyloP100		-0.27
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: rs3824755; hg19: chr10-104595849;