rs2241394
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000064.4(C3):c.3811-73C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,417,662 control chromosomes in the GnomAD database, including 11,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.10 ( 992 hom., cov: 32)
Exomes 𝑓: 0.12 ( 10267 hom. )
Consequence
C3
NM_000064.4 intron
NM_000064.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.606
Genes affected
C3 (HGNC:1318): (complement C3) Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form the mature protein, which is then further processed to generate numerous peptide products. The C3a peptide, also known as the C3a anaphylatoxin, modulates inflammation and possesses antimicrobial activity. Mutations in this gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 19-6685219-G-C is Benign according to our data. Variant chr19-6685219-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 162178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C3 | NM_000064.4 | c.3811-73C>G | intron_variant | ENST00000245907.11 | NP_000055.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C3 | ENST00000245907.11 | c.3811-73C>G | intron_variant | 1 | NM_000064.4 | ENSP00000245907.4 |
Frequencies
GnomAD3 genomes AF: 0.104 AC: 15835AN: 152048Hom.: 989 Cov.: 32
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GnomAD4 exome AF: 0.123 AC: 156028AN: 1265496Hom.: 10267 AF XY: 0.122 AC XY: 77303AN XY: 635006
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GnomAD4 genome AF: 0.104 AC: 15855AN: 152166Hom.: 992 Cov.: 32 AF XY: 0.105 AC XY: 7831AN XY: 74386
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2Other:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not provided, no classification provided | not provided | Department of Ophthalmology and Visual Sciences Kyoto University | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | This variant is associated with the following publications: (PMID: 22174912) - |
Kidney disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 12, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at