12-7108401-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016546.4(C1RL):āc.150G>Cā(p.Gln50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,613,944 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00020 ( 0 hom., cov: 32)
Exomes š: 0.00038 ( 1 hom. )
Consequence
C1RL
NM_016546.4 missense
NM_016546.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 1.73
Genes affected
C1RL (HGNC:21265): (complement C1r subcomponent like) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in zymogen activation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16176209).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C1RL | NM_016546.4 | c.150G>C | p.Gln50His | missense_variant | 2/6 | ENST00000266542.9 | NP_057630.2 | |
C1RL-AS1 | NR_026947.1 | n.94C>G | non_coding_transcript_exon_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C1RL | ENST00000266542.9 | c.150G>C | p.Gln50His | missense_variant | 2/6 | 1 | NM_016546.4 | ENSP00000266542 | P1 | |
C1RL-AS1 | ENST00000535078.2 | n.79C>G | non_coding_transcript_exon_variant | 1/7 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152246Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000116 AC: 29AN: 251032Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135672
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GnomAD4 exome AF: 0.000379 AC: 554AN: 1461698Hom.: 1 Cov.: 31 AF XY: 0.000380 AC XY: 276AN XY: 727132
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GnomAD4 genome AF: 0.000197 AC: 30AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74378
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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 | Dec 21, 2022 | The c.150G>C (p.Q50H) alteration is located in exon 2 (coding exon 2) of the C1RL gene. This alteration results from a G to C substitution at nucleotide position 150, causing the glutamine (Q) at amino acid position 50 to be replaced by a histidine (H). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;T;D;D
Sift4G
Uncertain
D;D;.;T
Polyphen
D;D;.;D
Vest4
MutPred
Gain of catalytic residue at L52 (P = 0);Gain of catalytic residue at L52 (P = 0);Gain of catalytic residue at L52 (P = 0);Gain of catalytic residue at L52 (P = 0);
MVP
MPC
ClinPred
T
GERP RS
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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