10-102836639-C-T

Variant names:

• chr10-102836639-C-T
• rs10786712
• NM_000102.4:c.297+426G>A

Variant summary

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

The NM_000102.4(CYP17A1):​c.297+426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 199,818 control chromosomes in the GnomAD database, including 14,476 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 0.39 (11490 hom., cov: 30)
  • Exomes 𝑓: 0.34 (2986 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 31 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.297+426G>A		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.297+426G>A		intron_variant	Intron 1 of 7	1	NM_000102.4	ENSP00000358903.3

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58556 AN: 151618 Hom.: 11480 Cov.: 30

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.339 AC: 16289 AN: 48082 Hom.: 2986 AF XY: 0.339 AC XY: 8444 AN XY: 24922

African (AFR) AF: 0.291 AC: 473 AN: 1624

American (AMR) AF: 0.365 AC: 1386 AN: 3798

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 356 AN: 1088

East Asian (EAS) AF: 0.492 AC: 1374 AN: 2792

South Asian (SAS) AF: 0.297 AC: 1787 AN: 6016

European-Finnish (FIN) AF: 0.317 AC: 455 AN: 1436

Middle Eastern (MID) AF: 0.311 AC: 51 AN: 164

European-Non Finnish (NFE) AF: 0.334 AC: 9599 AN: 28728

Other (OTH) AF: 0.332 AC: 808 AN: 2436

GnomAD4 genome AF: 0.386 AC: 58609 AN: 151736 Hom.: 11490 Cov.: 30 AF XY: 0.384 AC XY: 28472 AN XY: 74130

African (AFR) AF: 0.356 AC: 14708 AN: 41340

American (AMR) AF: 0.391 AC: 5969 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3470

East Asian (EAS) AF: 0.561 AC: 2881 AN: 5140

South Asian (SAS) AF: 0.352 AC: 1692 AN: 4810

European-Finnish (FIN) AF: 0.355 AC: 3743 AN: 10538

Middle Eastern (MID) AF: 0.372 AC: 108 AN: 290

European-Non Finnish (NFE) AF: 0.400 AC: 27127 AN: 67880

Other (OTH) AF: 0.389 AC: 818 AN: 2102

Alfa AF: 0.396 Hom.: 3354

Bravo AF: 0.390

Asia WGS AF: 0.408 AC: 1416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.45
PhyloP100		0.14
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: rs10786712; hg19: chr10-104596396;