rs1754533
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000562.3(C8A):āc.1503T>Cā(p.Pro501=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,614,104 control chromosomes in the GnomAD database, including 4,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.10 ( 1254 hom., cov: 33)
Exomes š: 0.058 ( 3523 hom. )
Consequence
C8A
NM_000562.3 synonymous
NM_000562.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.701
Genes affected
C8A (HGNC:1352): (complement C8 alpha chain) C8 is a component of the complement system and contains three polypeptides, alpha, beta and gamma. This gene encodes the alpha subunit of C8. C8 participates in the formation of the membrane attack complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause complement C8 alpha-gamma deficiency. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 1-56912525-T-C is Benign according to our data. Variant chr1-56912525-T-C is described in ClinVar as [Benign]. Clinvar id is 402463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.701 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C8A | NM_000562.3 | c.1503T>C | p.Pro501= | synonymous_variant | 10/11 | ENST00000361249.4 | NP_000553.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C8A | ENST00000361249.4 | c.1503T>C | p.Pro501= | synonymous_variant | 10/11 | 1 | NM_000562.3 | ENSP00000354458 | P4 |
Frequencies
GnomAD3 genomes AF: 0.102 AC: 15593AN: 152164Hom.: 1252 Cov.: 33
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GnomAD3 exomes AF: 0.0756 AC: 19000AN: 251452Hom.: 1073 AF XY: 0.0752 AC XY: 10218AN XY: 135910
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GnomAD4 exome AF: 0.0578 AC: 84518AN: 1461820Hom.: 3523 Cov.: 33 AF XY: 0.0596 AC XY: 43313AN XY: 727218
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GnomAD4 genome AF: 0.103 AC: 15615AN: 152284Hom.: 1254 Cov.: 33 AF XY: 0.102 AC XY: 7605AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at