9-120952753-A-G
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_001735.3(C5):āc.5017T>Cā(p.Leu1673Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000043 ( 0 hom. )
Consequence
C5
NM_001735.3 synonymous
NM_001735.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.398
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 -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 9-120952753-A-G is Benign according to our data. Variant chr9-120952753-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1640950.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.398 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C5 | NM_001735.3 | c.5017T>C | p.Leu1673Leu | synonymous_variant | 41/41 | ENST00000223642.3 | NP_001726.2 | |
C5 | NM_001317163.2 | c.5035T>C | p.Leu1679Leu | synonymous_variant | 41/41 | NP_001304092.1 | ||
C5-OT1 | NR_148450.1 | n.79T>C | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C5 | ENST00000223642.3 | c.5017T>C | p.Leu1673Leu | synonymous_variant | 41/41 | 1 | NM_001735.3 | ENSP00000223642.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251376Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135872
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GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461062Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 726854
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 13, 2023 | - - |
Computational scores
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Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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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