chr10-102830771-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_000102.4(CYP17A1):c.1458C>T(p.Ile486=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000444 in 1,600,214 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: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
CYP17A1
NM_000102.4 synonymous
NM_000102.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.75
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]
WBP1L (HGNC:23510): (WW domain binding protein 1 like) Predicted to enable ubiquitin protein ligase binding activity. Predicted to act upstream of or within CXCL12-activated CXCR4 signaling pathway; hemopoiesis; and positive regulation of protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 10-102830771-G-A is Benign according to our data. Variant chr10-102830771-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 755651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.75 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00023 (35/152222) while in subpopulation AFR AF= 0.000794 (33/41552). AF 95% confidence interval is 0.00058. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CYP17A1 | NM_000102.4 | c.1458C>T | p.Ile486= | synonymous_variant | 8/8 | ENST00000369887.4 | NP_000093.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CYP17A1 | ENST00000369887.4 | c.1458C>T | p.Ile486= | synonymous_variant | 8/8 | 1 | NM_000102.4 | ENSP00000358903 | P3 |
Frequencies
GnomAD3 genomes 0.000230 AC: 35AN: 152104Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000578 AC: 14AN: 242208Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 131090
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GnomAD4 exome AF: 0.0000249 AC: 36AN: 1447992Hom.: 0 Cov.: 28 AF XY: 0.0000194 AC XY: 14AN XY: 720476
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GnomAD4 genome 0.000230 AC: 35AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74432
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Deficiency of steroid 17-alpha-monooxygenase Uncertain:1Benign:1
| Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 08, 2021 | - - |
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 14, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at