rs1298248066
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004820.5(CYP7B1):āc.538C>Gā(p.Leu180Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,610 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L180L) has been classified as Likely benign.
Frequency
Consequence
NM_004820.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP7B1 | NM_004820.5 | c.538C>G | p.Leu180Val | missense_variant | 3/6 | ENST00000310193.4 | |
CYP7B1 | NM_001324112.2 | c.538C>G | p.Leu180Val | missense_variant | 3/7 | ||
CYP7B1 | XM_017014002.2 | c.604C>G | p.Leu202Val | missense_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP7B1 | ENST00000310193.4 | c.538C>G | p.Leu180Val | missense_variant | 3/6 | 1 | NM_004820.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251046Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135678
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461504Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727038
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74294
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 458230). This variant has not been reported in the literature in individuals affected with CYP7B1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 180 of the CYP7B1 protein (p.Leu180Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at