Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004326807 | SCV003989759 | uncertain significance | not specified | 2023-05-08 | criteria provided, single submitter | clinical testing | The c.889G>A (p.E297K) alteration is located in exon 6 (coding exon 6) of the CFHR1 gene. This alteration results from a G to A substitution at nucleotide position 889, causing the glutamic acid (E) at amino acid position 297 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004326807 | SCV005075792 | likely benign | not specified | 2024-04-03 | criteria provided, single submitter | clinical testing | Variant summary: CFHR1 c.889G>A (p.Glu297Lys) results in a conservative amino acid change located in the Sushi/SCR/CCP domain (IPR000436) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00036 in 237218 control chromosomes in the gnomAD database, including 12 homozygotes. The observed variant frequency is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in CFHR1 causing Genetic Atypical Hemolytic Uremic Syndrome phenotype (0.00016), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.889G>A in individuals affected with Genetic Atypical Hemolytic Uremic Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2554326). Based on the evidence outlined above, the variant was classified as likely benign. |