chr1-22659604-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001378156.1(C1QB):c.142G>A(p.Asp48Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C1QB | NM_001378156.1 | c.142G>A | p.Asp48Asn | missense_variant | 2/3 | ENST00000509305.6 | |
C1QB | NM_000491.5 | c.148G>A | p.Asp50Asn | missense_variant | 2/3 | ||
C1QB | NM_001371184.3 | c.142G>A | p.Asp48Asn | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C1QB | ENST00000509305.6 | c.142G>A | p.Asp48Asn | missense_variant | 2/3 | 1 | NM_001378156.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250326Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135376
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461570Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727074
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 08, 2021 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 (rs770317321, ExAC 0.009%). This sequence change replaces aspartic acid with asparagine at codon 50 of the C1QB protein (p.Asp50Asn). The aspartic acid residue is highly 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