rs398122868
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000066.4(C8B):c.1047_1048insGGCTGTG(p.Leu350GlyfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
C8B
NM_000066.4 frameshift
NM_000066.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.197
Genes affected
C8B (HGNC:1353): (complement C8 beta chain) This gene encodes one of the three subunits of the complement component 8 (C8) protein. C8 is composed of equimolar amounts of alpha, beta and gamma subunits, which are encoded by three separate genes. C8 is one component of the membrane attack complex, which mediates cell lysis, and it initiates membrane penetration of the complex. This protein mediates the interaction of C8 with the C5b-7 membrane attack complex precursor. In humans deficiency of this protein is associated with increased risk of meningococcal infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-56945878-G-GCACAGCC is Pathogenic according to our data. Variant chr1-56945878-G-GCACAGCC is described in ClinVar as [Pathogenic]. Clinvar id is 35597.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C8B | NM_000066.4 | c.1047_1048insGGCTGTG | p.Leu350GlyfsTer8 | frameshift_variant | 7/12 | ENST00000371237.9 | |
C8B | NM_001278543.2 | c.891_892insGGCTGTG | p.Leu298GlyfsTer8 | frameshift_variant | 8/13 | ||
C8B | NM_001278544.2 | c.861_862insGGCTGTG | p.Leu288GlyfsTer8 | frameshift_variant | 8/13 | ||
C8B | XM_047429957.1 | c.865-2055_865-2054insGGCTGTG | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C8B | ENST00000371237.9 | c.1047_1048insGGCTGTG | p.Leu350GlyfsTer8 | frameshift_variant | 7/12 | 1 | NM_000066.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 152136Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461838Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727226
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74304
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Type II complement component 8 deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2009 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at