chr1-22638945-A-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_015991.4(C1QA):c.276A>G(p.Gly92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,600,412 control chromosomes in the GnomAD database, including 154,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.51 ( 21743 hom., cov: 33)
Exomes 𝑓: 0.42 ( 133216 hom. )
Consequence
C1QA
NM_015991.4 synonymous
NM_015991.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.733
Genes affected
C1QA (HGNC:1241): (complement C1q A chain) This gene encodes the A-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. 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. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 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=-0.85).
BP6
Variant 1-22638945-A-G is Benign according to our data. Variant chr1-22638945-A-G is described in ClinVar as [Benign]. Clinvar id is 1167796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-22638945-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.733 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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C1QA | NM_015991.4 | c.276A>G | p.Gly92= | synonymous_variant | 3/3 | ENST00000374642.8 | |
C1QA | NM_001347465.2 | c.276A>G | p.Gly92= | synonymous_variant | 3/3 | ||
C1QA | NM_001347466.2 | c.276A>G | p.Gly92= | synonymous_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C1QA | ENST00000374642.8 | c.276A>G | p.Gly92= | synonymous_variant | 3/3 | 1 | NM_015991.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.512 AC: 77782AN: 151976Hom.: 21690 Cov.: 33
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GnomAD3 exomes AF: 0.486 AC: 107980AN: 222358Hom.: 27825 AF XY: 0.479 AC XY: 57767AN XY: 120698
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GnomAD4 exome AF: 0.420 AC: 608384AN: 1448318Hom.: 133216 Cov.: 83 AF XY: 0.423 AC XY: 304269AN XY: 719314
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GnomAD4 genome AF: 0.512 AC: 77891AN: 152094Hom.: 21743 Cov.: 33 AF XY: 0.518 AC XY: 38477AN XY: 74342
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 77% of patients studied by a panel of primary immunodeficiencies. Number of patients: 68. Only high quality variants are reported. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | This variant is associated with the following publications: (PMID: 26017655, 12630757, 16465510, 16086173, 20332777) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
C1Q deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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