7-75915137-A-C
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The ENST00000706544.1(POR):c.-47A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 154,052 control chromosomes in the GnomAD database, including 19,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.44 ( 19420 hom., cov: 33)
Exomes 𝑓: 0.31 ( 109 hom. )
Consequence
POR
ENST00000706544.1 5_prime_UTR
ENST00000706544.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.320
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 Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 7-75915137-A-C is Benign according to our data. Variant chr7-75915137-A-C is described in ClinVar as [Benign]. Clinvar id is 360686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-75915137-A-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POR | NM_001395413.1 | upstream_gene_variant | ENST00000461988.6 | NP_001382342.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POR | ENST00000461988.6 | upstream_gene_variant | 1 | NM_001395413.1 | ENSP00000419970 | P4 |
Frequencies
GnomAD3 genomes AF: 0.438 AC: 66601AN: 152044Hom.: 19374 Cov.: 33
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GnomAD4 exome AF: 0.308 AC: 584AN: 1896Hom.: 109 Cov.: 0 AF XY: 0.311 AC XY: 289AN XY: 930
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GnomAD4 genome AF: 0.438 AC: 66694AN: 152156Hom.: 19420 Cov.: 33 AF XY: 0.435 AC XY: 32322AN XY: 74382
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
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 | Mar 03, 2015 | - - |
Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at