chr1-22659588-T-TG
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001378156.1(C1QB):c.129dup(p.Thr44AspfsTer28) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000131 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Consequence
C1QB
NM_001378156.1 frameshift
NM_001378156.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.01
Genes affected
C1QB (HGNC:1242): (complement C1q B chain) This gene encodes the B-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q is composed of 18 polypeptide chains which include 6 A-chains, 6 B-chains, and 6 C-chains. Each chain contains an N-terminal collagen-like region and a C-terminal C1q globular domain. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C1QB | NM_001378156.1 | c.129dup | p.Thr44AspfsTer28 | frameshift_variant | 2/3 | ENST00000509305.6 | |
C1QB | NM_000491.5 | c.135dup | p.Thr46AspfsTer28 | frameshift_variant | 2/3 | ||
C1QB | NM_001371184.3 | c.129dup | p.Thr44AspfsTer28 | frameshift_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C1QB | ENST00000509305.6 | c.129dup | p.Thr44AspfsTer28 | frameshift_variant | 2/3 | 1 | NM_001378156.1 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 32
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change creates a premature translational stop signal (p.Thr46Aspfs*28) in the C1QB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 208 amino acid(s) of the C1QB protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with C1QB-related conditions. ClinVar contains an entry for this variant (Variation ID: 1483546). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at