10-102835149-T-C

Variant names:

• chr10-102835149-T-C
• rs743575
• NM_000102.4:c.436+105A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000102.4(CYP17A1):​c.436+105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,005,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.415
• Publications: 12 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-102835149-T-C is Benign according to our data. Variant chr10-102835149-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 795103.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.436+105A>G		intron_variant	Intron 2 of 7	ENST00000369887.4	NP_000093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4	c.436+105A>G		intron_variant	Intron 2 of 7	1	NM_000102.4	ENSP00000358903.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000199 AC: 2 AN: 1005288 Hom.: 0 Cov.: 14 AF XY: 0.00000193 AC XY: 1 AN XY: 517444

African (AFR) AF: 0.00 AC: 0 AN: 24864

American (AMR) AF: 0.00 AC: 0 AN: 43420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22784

East Asian (EAS) AF: 0.0000534 AC: 2 AN: 37484

South Asian (SAS) AF: 0.00 AC: 0 AN: 76692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 707360

Other (OTH) AF: 0.00 AC: 0 AN: 45462

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 515

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 29, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		-0.41

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: rs743575; hg19: chr10-104594906;