NM_000102.4:c.298-271A>C

Variant names:

• chr10-102835663-T-G
• rs3781287
• NM_000102.4:c.298-271A>C

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.298-271A>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
• Publications: 24 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=-0.92).
• BP6: Variant 10-102835663-T-G is Benign according to our data. Variant chr10-102835663-T-G is described in ClinVar as Benign. ClinVar VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	NM_000102.4	MANE Select	c.298-271A>C		intron	N/A	NP_000093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	ENST00000369887.4	TSL:1 MANE Select	c.298-271A>C		intron	N/A	ENSP00000358903.3
	CYP17A1	ENST00000639393.1	TSL:5	c.298-271A>C		intron	N/A	ENSP00000492651.1
	CYP17A1	ENST00000638971.1	TSL:5	c.298-271A>C		intron	N/A	ENSP00000492313.1

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

African (AFR) AF: 0.377 AC: 3660 AN: 9720

American (AMR) AF: 0.404 AC: 6150 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 4292 AN: 10122

East Asian (EAS) AF: 0.514 AC: 10484 AN: 20402

South Asian (SAS) AF: 0.481 AC: 20933 AN: 43564

European-Finnish (FIN) AF: 0.382 AC: 6999 AN: 18324

Middle Eastern (MID) AF: 0.437 AC: 615 AN: 1406

European-Non Finnish (NFE) AF: 0.410 AC: 81018 AN: 197488

Other (OTH) AF: 0.413 AC: 7850 AN: 19000

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

African (AFR) AF: 0.375 AC: 15543 AN: 41470

American (AMR) AF: 0.405 AC: 6195 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1531 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2907 AN: 5162

South Asian (SAS) AF: 0.469 AC: 2264 AN: 4824

European-Finnish (FIN) AF: 0.358 AC: 3785 AN: 10570

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28313 AN: 67970

Other (OTH) AF: 0.412 AC: 871 AN: 2112

Alfa AF: 0.409 Hom.: 36649

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

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.33
PhyloP100		-0.53
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: rs3781287; hg19: chr10-104595420;