rs201223301
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_006587.4(CORIN):c.1615C>T(p.Arg539Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,610,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
CORIN
NM_006587.4 missense
NM_006587.4 missense
Scores
13
3
3
Clinical Significance
Conservation
PhyloP100: 5.67
Genes affected
CORIN (HGNC:19012): (corin, serine peptidase) This gene encodes a member of the type II transmembrane serine protease class of the trypsin superfamily. Members of this family are composed of multiple structurally distinct domains. The encoded protein converts pro-atrial natriuretic peptide to biologically active atrial natriuretic peptide, a cardiac hormone that regulates blood volume and pressure. This protein may also function as a pro-brain-type natriuretic peptide convertase. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.933
BS2
?
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CORIN | NM_006587.4 | c.1615C>T | p.Arg539Cys | missense_variant | 12/22 | ENST00000273857.9 | |
CORIN | NM_001278585.2 | c.1303C>T | p.Arg435Cys | missense_variant | 10/20 | ||
CORIN | NM_001278586.2 | c.1504C>T | p.Arg502Cys | missense_variant | 11/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CORIN | ENST00000273857.9 | c.1615C>T | p.Arg539Cys | missense_variant | 12/22 | 1 | NM_006587.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152194Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000802 AC: 20AN: 249304Hom.: 0 AF XY: 0.0000594 AC XY: 8AN XY: 134656
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GnomAD4 exome AF: 0.000137 AC: 200AN: 1457978Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 88AN XY: 724746
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74340
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Asia WGS
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Variant of unknown significance Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Mar 15, 2013 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;.;T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;.;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
D;.;.;.;.;.
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