chr4-47623631-A-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006587.4(CORIN):āc.2480T>Cā(p.Ile827Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000066 ( 0 hom., cov: 32)
Exomes š: 0.00011 ( 0 hom. )
Consequence
CORIN
NM_006587.4 missense
NM_006587.4 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 6.79
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 -4 ACMG points.
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CORIN | NM_006587.4 | c.2480T>C | p.Ile827Thr | missense_variant | 19/22 | ENST00000273857.9 | |
CORIN | NM_001278585.2 | c.2168T>C | p.Ile723Thr | missense_variant | 17/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CORIN | ENST00000273857.9 | c.2480T>C | p.Ile827Thr | missense_variant | 19/22 | 1 | NM_006587.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152226Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251308Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135806
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GnomAD4 exome AF: 0.000106 AC: 155AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.000105 AC XY: 76AN XY: 727234
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74364
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | The c.2480T>C (p.I827T) alteration is located in exon 19 (coding exon 19) of the CORIN gene. This alteration results from a T to C substitution at nucleotide position 2480, causing the isoleucine (I) at amino acid position 827 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;T;T;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;N;N;N
REVEL
Pathogenic
Sift
Benign
D;.;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
P;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
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