chr8-64798532-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004820.5(CYP7B1):āc.56T>Cā(p.Leu19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,499,110 control chromosomes in the GnomAD database, including 645 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L19R) has been classified as Uncertain significance.
Frequency
Consequence
NM_004820.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP7B1 | NM_004820.5 | c.56T>C | p.Leu19Pro | missense_variant | 1/6 | ENST00000310193.4 | |
CYP7B1 | NM_001324112.2 | c.56T>C | p.Leu19Pro | missense_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP7B1 | ENST00000310193.4 | c.56T>C | p.Leu19Pro | missense_variant | 1/6 | 1 | NM_004820.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0386 AC: 5872AN: 152134Hom.: 377 Cov.: 33
GnomAD3 exomes AF: 0.00302 AC: 289AN: 95666Hom.: 10 AF XY: 0.00230 AC XY: 124AN XY: 53878
GnomAD4 exome AF: 0.00352 AC: 4739AN: 1346868Hom.: 269 Cov.: 32 AF XY: 0.00303 AC XY: 2011AN XY: 664370
GnomAD4 genome AF: 0.0386 AC: 5877AN: 152242Hom.: 376 Cov.: 33 AF XY: 0.0372 AC XY: 2772AN XY: 74436
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 14, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 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. - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 12, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 02, 2018 | - - |
Hereditary spastic paraplegia 5A Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at