chr6-32027362-A-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001002029.4(C4B):c.2719A>G(p.Thr907Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
C4B
NM_001002029.4 missense
NM_001002029.4 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: 1.08
Genes affected
C4B (HGNC:1324): (complement C4B (Chido/Rodgers blood group)) This gene encodes the basic form of complement factor 4, and together with the C4A gene, is part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, C4B
BP4
?
Computational evidence support a benign effect (MetaRNN=0.040878892).
BP6
?
Variant 6-32027362-A-G is Benign according to our data. Variant chr6-32027362-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1284968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-32027362-A-G is described in Lovd as [Benign]. Variant chr6-32027362-A-G is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C4B | NM_001002029.4 | c.2719A>G | p.Thr907Ala | missense_variant | 21/41 | ENST00000435363.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C4B | ENST00000435363.7 | c.2719A>G | p.Thr907Ala | missense_variant | 21/41 | 1 | NM_001002029.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 39964Hom.: 0 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.0000580 AC: 4AN: 68936Hom.: 0 AF XY: 0.0000537 AC XY: 2AN XY: 37218
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000171 AC: 1AN: 583616Hom.: 0 Cov.: 5 AF XY: 0.00000352 AC XY: 1AN XY: 284100
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 39964Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 18614
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N;N
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.0
.;B
Vest4
MutPred
Loss of glycosylation at T907 (P = 0.0767);Loss of glycosylation at T907 (P = 0.0767);
MVP
ClinPred
T
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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