rs2274700
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000186.4(CFH):c.1419G>A(p.Ala473Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,610,552 control chromosomes in the GnomAD database, including 145,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A473A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000186.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFH | NM_000186.4 | c.1419G>A | p.Ala473Ala | synonymous_variant | Exon 10 of 22 | ENST00000367429.9 | NP_000177.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFH | ENST00000367429.9 | c.1419G>A | p.Ala473Ala | synonymous_variant | Exon 10 of 22 | 1 | NM_000186.4 | ENSP00000356399.4 | ||
ENSG00000289697 | ENST00000696032.1 | c.1419G>A | p.Ala473Ala | synonymous_variant | Exon 10 of 27 | ENSP00000512341.1 |
Frequencies
GnomAD3 genomes AF: 0.439 AC: 66624AN: 151640Hom.: 14776 Cov.: 31
GnomAD3 exomes AF: 0.444 AC: 111026AN: 250332Hom.: 25005 AF XY: 0.448 AC XY: 60592AN XY: 135286
GnomAD4 exome AF: 0.420 AC: 613118AN: 1458796Hom.: 130822 Cov.: 32 AF XY: 0.424 AC XY: 308017AN XY: 725824
GnomAD4 genome AF: 0.439 AC: 66678AN: 151756Hom.: 14793 Cov.: 31 AF XY: 0.446 AC XY: 33037AN XY: 74146
ClinVar
Submissions by phenotype
not provided Benign:3
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This variant is associated with the following publications: (PMID: 25087612, 21868097, 22848687, 16299065) -
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Hemolytic uremic syndrome, atypical, susceptibility to, 1 Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
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Age related macular degeneration 4 Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
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Basal laminar drusen Benign:2
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Factor H deficiency Benign:1
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CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
Atypical hemolytic-uremic syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at