chr9-120963693-C-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001735.3(C5):c.4266G>A(p.Ala1422=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,613,500 control chromosomes in the GnomAD database, including 2,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.071 ( 888 hom., cov: 32)
Exomes 𝑓: 0.025 ( 2035 hom. )
Consequence
C5
NM_001735.3 synonymous
NM_001735.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.648
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 -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 9-120963693-C-T is Benign according to our data. Variant chr9-120963693-C-T is described in ClinVar as [Benign]. Clinvar id is 1167627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.648 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C5 | NM_001735.3 | c.4266G>A | p.Ala1422= | synonymous_variant | 34/41 | ENST00000223642.3 | |
C5 | NM_001317163.2 | c.4284G>A | p.Ala1428= | synonymous_variant | 34/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C5 | ENST00000223642.3 | c.4266G>A | p.Ala1422= | synonymous_variant | 34/41 | 1 | NM_001735.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0711 AC: 10809AN: 151976Hom.: 884 Cov.: 32
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GnomAD3 exomes AF: 0.0450 AC: 11301AN: 251344Hom.: 758 AF XY: 0.0417 AC XY: 5658AN XY: 135840
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GnomAD4 exome AF: 0.0249 AC: 36327AN: 1461406Hom.: 2035 Cov.: 30 AF XY: 0.0251 AC XY: 18282AN XY: 727030
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GnomAD4 genome AF: 0.0713 AC: 10838AN: 152094Hom.: 888 Cov.: 32 AF XY: 0.0712 AC XY: 5292AN XY: 74364
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
C5-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 01, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at