chr10-102835663-T-G

Position:

• chr10-102835663-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000102.4(CYP17A1):​c.298-271A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 487,324 control chromosomes in the GnomAD database, including 43,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12701 hom., cov: 32)
  • Exomes 𝑓: 0.42 (30504 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.533

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-102835663-T-G is Benign according to our data. Variant chr10-102835663-T-G is described in ClinVar as [Benign]. Clinvar id is 1276128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.298-271A>C		intron_variant		ENST00000369887.4	NP_000093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4	c.298-271A>C		intron_variant		1	NM_000102.4	ENSP00000358903	P3

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61659 AN: 151958 Hom.: 12692 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.424 AC: 142001 AN: 335248 Hom.: 30504 AF XY: 0.429 AC XY: 76187 AN XY: 177676

Gnomad4 AFR exome AF: 0.377

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.481

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.413

GnomAD4 genome AF: 0.406 AC: 61711 AN: 152076 Hom.: 12701 Cov.: 32 AF XY: 0.404 AC XY: 30022 AN XY: 74316

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.412

Alfa AF: 0.410 Hom.: 21963

Bravo AF: 0.407

Asia WGS AF: 0.466 AC: 1617 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.33

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: rs3781287; hg19: chr10-104595420;