chr1-207124265-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000715.4(C4BPA):c.605G>T(p.Ser202Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,682 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )
Consequence
C4BPA
NM_000715.4 missense
NM_000715.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: -0.291
Genes affected
C4BPA (HGNC:1325): (complement component 4 binding protein alpha) This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. Along with a single, unique beta-chain, seven identical alpha-chains encoded by this gene assemble into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. Two pseudogenes of this gene are also found in the cluster. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C4BPA | NM_000715.4 | c.605G>T | p.Ser202Ile | missense_variant | 6/12 | ENST00000367070.8 | |
C4BPA | XM_005273251.3 | c.605G>T | p.Ser202Ile | missense_variant | 6/12 | ||
C4BPA | XM_005273252.5 | c.605G>T | p.Ser202Ile | missense_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C4BPA | ENST00000367070.8 | c.605G>T | p.Ser202Ile | missense_variant | 6/12 | 1 | NM_000715.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250866Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135556
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GnomAD4 exome AF: 0.0000623 AC: 91AN: 1461574Hom.: 0 Cov.: 33 AF XY: 0.0000743 AC XY: 54AN XY: 727100
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74286
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2023 | The c.605G>T (p.S202I) alteration is located in exon 6 (coding exon 5) of the C4BPA gene. This alteration results from a G to T substitution at nucleotide position 605, causing the serine (S) at amino acid position 202 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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