chr1-22659523-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001378156.1(C1QB):c.61G>A(p.Asp21Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001378156.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C1QB | NM_001378156.1 | c.61G>A | p.Asp21Asn | missense_variant | 2/3 | ENST00000509305.6 | |
C1QB | NM_000491.5 | c.67G>A | p.Asp23Asn | missense_variant | 2/3 | ||
C1QB | NM_001371184.3 | c.61G>A | p.Asp21Asn | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C1QB | ENST00000509305.6 | c.61G>A | p.Asp21Asn | missense_variant | 2/3 | 1 | NM_001378156.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251312Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135830
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461828Hom.: 0 Cov.: 32 AF XY: 0.0000371 AC XY: 27AN XY: 727218
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74266
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 20, 2023 | The c.67G>A (p.D23N) alteration is located in exon 2 (coding exon 1) of the C1QB gene. This alteration results from a G to A substitution at nucleotide position 67, causing the aspartic acid (D) at amino acid position 23 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2020 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with C1QB-related conditions. This variant is present in population databases (rs555943495, ExAC 0.02%). This sequence change replaces aspartic acid with asparagine at codon 23 of the C1QB protein (p.Asp23Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at