chr1-196743552-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000186.4(CFH):c.3234G>T(p.Arg1078Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.
Frequency
Consequence
NM_000186.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFH | NM_000186.4 | c.3234G>T | p.Arg1078Ser | missense_variant | 20/22 | ENST00000367429.9 | NP_000177.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFH | ENST00000367429.9 | c.3234G>T | p.Arg1078Ser | missense_variant | 20/22 | 1 | NM_000186.4 | ENSP00000356399.4 | ||
ENSG00000289697 | ENST00000696032.1 | c.3234G>T | p.Arg1078Ser | missense_variant | 20/27 | ENSP00000512341.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251440Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135894
GnomAD4 exome AF: 0.0000684 AC: 100AN: 1461726Hom.: 0 Cov.: 33 AF XY: 0.0000688 AC XY: 50AN XY: 727162
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 24, 2022 | - - |
Basal laminar drusen Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2008 | - - |
Factor H deficiency;C0730295:Basal laminar drusen;C1853147:Age related macular degeneration 4;C2749604:Hemolytic uremic syndrome, atypical, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jun 05, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at