chr4-107932139-C-T
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_183075.3(CYP2U1):c.490+6C>T 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 0.0195 in 1,600,114 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 23 hom., cov: 33)
Exomes 𝑓: 0.020 ( 331 hom. )
Consequence
CYP2U1
NM_183075.3 splice_donor_region, intron
NM_183075.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0002490
2
Clinical Significance
Conservation
PhyloP100: 0.763
Genes affected
CYP2U1 (HGNC:20582): (cytochrome P450 family 2 subfamily U 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 enzyme is a hydroxylase that metabolizes arachidonic acid, docosahexaenoic acid, and other long chain fatty acids. [provided by RefSeq, Jul 2008]
CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)
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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=-0.27).
BP6
?
Variant 4-107932139-C-T is Benign according to our data. Variant chr4-107932139-C-T is described in ClinVar as [Benign]. Clinvar id is 242188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2256/152284) while in subpopulation NFE AF= 0.0232 (1575/68024). AF 95% confidence interval is 0.0222. There are 23 homozygotes in gnomad4. There are 1113 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 23 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP2U1 | NM_183075.3 | c.490+6C>T | splice_donor_region_variant, intron_variant | ENST00000332884.11 | |||
LOC107986298 | XR_001741784.2 | n.205-21590G>A | intron_variant, non_coding_transcript_variant | ||||
CYP2U1-AS1 | NR_125929.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP2U1 | ENST00000332884.11 | c.490+6C>T | splice_donor_region_variant, intron_variant | 1 | NM_183075.3 | P1 | |||
CYP2U1-AS1 | ENST00000656249.1 | n.81-21590G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0148 AC: 2257AN: 152168Hom.: 23 Cov.: 33
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GnomAD3 exomes AF: 0.0166 AC: 3648AN: 219440Hom.: 47 AF XY: 0.0169 AC XY: 2038AN XY: 120904
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GnomAD4 exome AF: 0.0200 AC: 28899AN: 1447830Hom.: 331 Cov.: 31 AF XY: 0.0198 AC XY: 14246AN XY: 719108
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 02, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 22, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at