rs10985126
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001735.3(C5):āc.1155A>Gā(p.Gly385Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,612,844 control chromosomes in the GnomAD database, including 30,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.23 ( 4847 hom., cov: 32)
Exomes š: 0.18 ( 25887 hom. )
Consequence
C5
NM_001735.3 synonymous
NM_001735.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.109
Genes affected
C5 (HGNC:1331): (complement C5) This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge. Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 9-121021656-T-C is Benign according to our data. Variant chr9-121021656-T-C is described in ClinVar as [Benign]. Clinvar id is 402457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-121021656-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.109 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C5 | NM_001735.3 | c.1155A>G | p.Gly385Gly | synonymous_variant | 11/41 | ENST00000223642.3 | NP_001726.2 | |
C5 | NM_001317163.2 | c.1173A>G | p.Gly391Gly | synonymous_variant | 11/41 | NP_001304092.1 | ||
C5 | NM_001317164.2 | c.1155A>G | p.Gly385Gly | synonymous_variant | 11/21 | NP_001304093.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.230 AC: 34914AN: 151948Hom.: 4845 Cov.: 32
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GnomAD3 exomes AF: 0.176 AC: 44324AN: 251482Hom.: 4784 AF XY: 0.170 AC XY: 23109AN XY: 135914
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GnomAD4 exome AF: 0.180 AC: 263495AN: 1460778Hom.: 25887 Cov.: 32 AF XY: 0.178 AC XY: 129150AN XY: 726820
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GnomAD4 genome AF: 0.230 AC: 34956AN: 152066Hom.: 4847 Cov.: 32 AF XY: 0.224 AC XY: 16622AN XY: 74332
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at