rs797045899
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_001395413.1(POR):c.1239+10del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000222 in 1,577,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000024 ( 0 hom. )
Consequence
POR
NM_001395413.1 splice_donor_region, intron
NM_001395413.1 splice_donor_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.02
Genes affected
POR (HGNC:9208): (cytochrome p450 oxidoreductase) This gene encodes an endoplasmic reticulum membrane oxidoreductase that is essential for multiple metabolic processes, including reactions catalyzed by cytochrome P450 proteins for metabolism of steroid hormones, drugs and xenobiotics. The encoded protein has a flavin adenine dinucleotide (FAD)-binding domain and a flavodoxin-like domain which bind two cofactors, FAD and FMN, that allow it to donate electrons directly from NADPH to all microsomal P450 enzymes. Mutations in this gene cause a complex set of disorders, including apparent combined P450C17 and P450C21 deficiency, amenorrhea and disordered steroidogenesis, congenital adrenal hyperplasia and Antley-Bixler syndrome, that resemble those caused by defects in steroid metabolizing enzymes such as aromatase, 21-hydroxylase, and 17 alpha-hydroxylase. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 7-75984963-GC-G is Benign according to our data. Variant chr7-75984963-GC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211952.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POR | NM_001395413.1 | c.1239+10del | splice_donor_region_variant, intron_variant | ENST00000461988.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POR | ENST00000461988.6 | c.1239+10del | splice_donor_region_variant, intron_variant | 1 | NM_001395413.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151722Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000450 AC: 1AN: 222388Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 121106
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GnomAD4 exome AF: 0.0000239 AC: 34AN: 1425456Hom.: 0 Cov.: 44 AF XY: 0.0000184 AC XY: 13AN XY: 704846
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GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151722Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74120
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 13, 2015 | - - |
Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2023 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at