rs2269067
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001735.3(C5):c.4017+17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,602,582 control chromosomes in the GnomAD database, including 41,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.30 ( 9148 hom., cov: 32)
Exomes 𝑓: 0.20 ( 32613 hom. )
Consequence
C5
NM_001735.3 intron
NM_001735.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.465
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 9-120974762-G-C is Benign according to our data. Variant chr9-120974762-G-C is described in ClinVar as [Benign]. Clinvar id is 1166860.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-120974762-G-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C5 | NM_001735.3 | c.4017+17C>G | intron_variant | ENST00000223642.3 | |||
C5 | NM_001317163.2 | c.4035+17C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C5 | ENST00000223642.3 | c.4017+17C>G | intron_variant | 1 | NM_001735.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.296 AC: 44933AN: 151936Hom.: 9119 Cov.: 32
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GnomAD3 exomes AF: 0.203 AC: 50935AN: 251358Hom.: 6903 AF XY: 0.193 AC XY: 26250AN XY: 135868
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GnomAD4 exome AF: 0.198 AC: 287559AN: 1450528Hom.: 32613 Cov.: 30 AF XY: 0.195 AC XY: 140863AN XY: 722452
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GnomAD4 genome ? AF: 0.296 AC: 45011AN: 152054Hom.: 9148 Cov.: 32 AF XY: 0.288 AC XY: 21395AN XY: 74352
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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