NM_006587.4:c.2047A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006587.4(CORIN):c.2047A>T(p.Ser683Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,614,112 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 31 hom. )

Consequence

CORIN
NM_006587.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.90

Publications

4 publications found

Variant links:

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]

CORIN Gene-Disease associations (from GenCC):

preeclampsia/eclampsia 5
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CORIN links:

LOC105374444 (HGNC:):

LOC105374444 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016170084).

BP6

Variant 4-47643167-T-A is Benign according to our data. Variant chr4-47643167-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 811600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4 link	c.2047A>T	p.Ser683Cys	missense_variant	Exon 15 of 22	ENST00000273857.9	NP_006578.2	Q9Y5Q5-1B4E2W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9 link	c.2047A>T	p.Ser683Cys	missense_variant	Exon 15 of 22	1	NM_006587.4	ENSP00000273857.4		Q9Y5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

374

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00974

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00343

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00350

AC:

878

AN:

250928

AF XY:

0.00403

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00333

Gnomad OTH exome

AF:

0.00360

GnomAD4 exome

AF:

0.00413

AC:

6033

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

3195

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.000538

AC:

AN:

33474

American (AMR)

AF:

0.00192

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.000803

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39688

South Asian (SAS)

AF:

0.0125

AC:

1074

AN:

86258

European-Finnish (FIN)

AF:

0.000505

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00920

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00404

AC:

4497

AN:

1111958

Other (OTH)

AF:

0.00422

AC:

255

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

351

702

1053

1404

1755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

186

372

558

744

930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00246

AC:

374

AN:

152308

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41582

American (AMR)

AF:

0.00359

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00975

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00343

AC:

233

AN:

68012

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00298

Hom.:

Bravo

AF:

0.00225

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00338

AC:

410

Asia WGS

AF:

0.00347

AC:

AN:

3476

EpiCase

AF:

0.00349

EpiControl

AF:

0.00368

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Preeclampsia/eclampsia 5

Benign:1

Dec 26, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Pathogenic

0.90

D;.;.;D;.;D

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

T;T;T;T;T;D

MetaRNN

Benign

0.016

T;T;T;T;T;T

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.1

M;.;.;.;.;.

PhyloP100

2.9

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.2

D;.;D;D;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0060

D;.;D;D;D;T

Sift4G

Uncertain

0.0080

D;D;D;D;D;D

Polyphen

1.0

D;.;.;.;.;.

Vest4

0.53

MVP

1.0

MPC

0.33

ClinPred

0.026

GERP RS

2.6

Varity_R

0.15

gMVP

0.73

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over