10-102836639-C-T

Position:

• chr10-102836639-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.297+426G>A		intron_variant		ENST00000369887.4	NP_000093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4	c.297+426G>A		intron_variant		1	NM_000102.4	ENSP00000358903	P3

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

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.332

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

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.389

Alfa AF: 0.397 Hom.: 1914

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10786712; hg19: chr10-104596396;