rs796052138
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_000186.4(CFH):c.671_673del(p.Lys224del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Consequence
CFH
NM_000186.4 inframe_deletion
NM_000186.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.56
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_000186.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 1-196679670-CAGA-C is Pathogenic according to our data. Variant chr1-196679670-CAGA-C is described in ClinVar as [Pathogenic]. Clinvar id is 16555.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFH | NM_000186.4 | c.671_673del | p.Lys224del | inframe_deletion | 6/22 | ENST00000367429.9 | |
CFH | NM_001014975.3 | c.671_673del | p.Lys224del | inframe_deletion | 6/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFH | ENST00000367429.9 | c.671_673del | p.Lys224del | inframe_deletion | 6/22 | 1 | NM_000186.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Factor H deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2006 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 6
DS_AL_spliceai
Position offset: -47
Find out detailed SpliceAI scores and Pangolin per-transcript scores at