chr1-22659564-C-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001378156.1(C1QB):c.102C>G(p.Ala34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000983 in 1,614,072 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0052 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 6 hom. )
Consequence
C1QB
NM_001378156.1 synonymous
NM_001378156.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.38
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 1-22659564-C-G is Benign according to our data. Variant chr1-22659564-C-G is described in ClinVar as [Benign]. Clinvar id is 725822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-22659564-C-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.38 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00523 (796/152292) while in subpopulation AFR AF= 0.0175 (726/41544). AF 95% confidence interval is 0.0164. There are 6 homozygotes in gnomad4. There are 363 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C1QB | NM_001378156.1 | c.102C>G | p.Ala34= | synonymous_variant | 2/3 | ENST00000509305.6 | |
C1QB | NM_000491.5 | c.108C>G | p.Ala36= | synonymous_variant | 2/3 | ||
C1QB | NM_001371184.3 | c.102C>G | p.Ala34= | synonymous_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C1QB | ENST00000509305.6 | c.102C>G | p.Ala34= | synonymous_variant | 2/3 | 1 | NM_001378156.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00523 AC: 796AN: 152174Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00140 AC: 351AN: 251016Hom.: 1 AF XY: 0.000921 AC XY: 125AN XY: 135720
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GnomAD4 exome AF: 0.000541 AC: 791AN: 1461780Hom.: 6 Cov.: 32 AF XY: 0.000459 AC XY: 334AN XY: 727196
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
C1QB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 05, 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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