rs372968576
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000066.4(C8B):c.336delC(p.Asn113ThrfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000066.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C8B | NM_000066.4 | c.336delC | p.Asn113ThrfsTer22 | frameshift_variant | Exon 3 of 12 | ENST00000371237.9 | NP_000057.3 | |
C8B | NM_001278543.2 | c.180delC | p.Asn61ThrfsTer22 | frameshift_variant | Exon 4 of 13 | NP_001265472.2 | ||
C8B | NM_001278544.2 | c.150delC | p.Asn51ThrfsTer22 | frameshift_variant | Exon 4 of 13 | NP_001265473.2 | ||
C8B | XM_047429957.1 | c.336delC | p.Asn113ThrfsTer22 | frameshift_variant | Exon 3 of 7 | XP_047285913.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251268Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135784
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461854Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5AN XY: 727230
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74326
ClinVar
Submissions by phenotype
Type II complement component 8 deficiency Pathogenic:1
- -
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Asn113Thrfs*22) in the C8B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in C8B are known to be pathogenic (PMID: 7594510). This variant is present in population databases (rs372968576, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with C8 beta deficiency (PMID: 7594510). This variant is also known as deletion at base 430. ClinVar contains an entry for this variant (Variation ID: 35595). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at