rs147226792
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BS1_Supporting
The NM_001735.3(C5):āc.1711C>Gā(p.Leu571Val) variant causes a missense change. The variant allele was found at a frequency of 0.000162 in 1,612,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L571L) has been classified as Likely benign.
Frequency
Consequence
NM_001735.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C5 | NM_001735.3 | c.1711C>G | p.Leu571Val | missense_variant | 13/41 | ENST00000223642.3 | |
C5 | NM_001317163.2 | c.1729C>G | p.Leu577Val | missense_variant | 13/41 | ||
C5 | NM_001317164.2 | c.1711C>G | p.Leu571Val | missense_variant | 13/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C5 | ENST00000223642.3 | c.1711C>G | p.Leu571Val | missense_variant | 13/41 | 1 | NM_001735.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000223 AC: 56AN: 251004Hom.: 0 AF XY: 0.000280 AC XY: 38AN XY: 135668
GnomAD4 exome AF: 0.000166 AC: 243AN: 1460232Hom.: 0 Cov.: 31 AF XY: 0.000193 AC XY: 140AN XY: 726492
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74486
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2022 | The c.1711C>G (p.L571V) alteration is located in exon 13 (coding exon 13) of the C5 gene. This alteration results from a C to G substitution at nucleotide position 1711, causing the leucine (L) at amino acid position 571 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Complement component 5 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 15, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 571 of the C5 protein (p.Leu571Val). This variant is present in population databases (rs147226792, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with C5-related conditions. ClinVar contains an entry for this variant (Variation ID: 548014). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt C5 protein function. 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. - |
C5-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 25, 2023 | The C5 c.1711C>G variant is predicted to result in the amino acid substitution p.Leu571Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.085% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-123779926-G-C). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at