rs796052137
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000186.4(CFH):c.83_86del(p.Arg28IlefsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as risk factor (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CFH
NM_000186.4 frameshift
NM_000186.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.11
Genes affected
CFH (HGNC:4883): (complement factor H) This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 103 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFH | NM_000186.4 | c.83_86del | p.Arg28IlefsTer5 | frameshift_variant | 2/22 | ENST00000367429.9 | |
CFH | NM_001014975.3 | c.83_86del | p.Arg28IlefsTer5 | frameshift_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFH | ENST00000367429.9 | c.83_86del | p.Arg28IlefsTer5 | frameshift_variant | 2/22 | 1 | NM_000186.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461698Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727144
GnomAD4 exome
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2
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1461698
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1
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727144
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hemolytic uremic syndrome, atypical, susceptibility to, 1 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Apr 01, 1998 | - - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at