dbSNP rs2289433: CORIN:p.Cys13Tyr (chr4-47837912-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006587.4(CORIN):c.38G>A(p.Cys13Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,613,360 control chromosomes in the GnomAD database, including 449,782 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 39499 hom., cov: 32)

Exomes 𝑓: 0.75 ( 410283 hom. )

Consequence

CORIN
NM_006587.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.739

Publications

41 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:

ENSG00000282917 (HGNC:):

ENSG00000282917 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.7607765E-7).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4 link	c.38G>A	p.Cys13Tyr	missense_variant	Exon 1 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.38G>A	p.Cys13Tyr	missense_variant	Exon 1 of 22	1	NM_006587.4	ENSP00000273857.4		Q9Y5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108861

AN:

152000

Hom.:

39464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.793

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.757

Gnomad FIN

AF:

0.839

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.754

Gnomad OTH

AF:

0.700

GnomAD2 exomes

AF:

0.738

AC:

185245

AN:

250996

AF XY:

0.739

show subpopulations

Gnomad AFR exome

AF:

0.617

Gnomad AMR exome

AF:

0.751

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.631

Gnomad FIN exome

AF:

0.829

Gnomad NFE exome

AF:

0.752

Gnomad OTH exome

AF:

0.743

GnomAD4 exome

AF:

0.748

AC:

1093049

AN:

1461242

Hom.:

410283

Cov.:

AF XY:

0.748

AC XY:

543700

AN XY:

726950

show subpopulations

African (AFR)

AF:

0.603

AC:

20200

AN:

33474

American (AMR)

AF:

0.749

AC:

33497

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

17368

AN:

26136

East Asian (EAS)

AF:

0.646

AC:

25629

AN:

39694

South Asian (SAS)

AF:

0.759

AC:

65435

AN:

86236

European-Finnish (FIN)

AF:

0.831

AC:

44080

AN:

53074

Middle Eastern (MID)

AF:

0.701

AC:

4009

AN:

5722

European-Non Finnish (NFE)

AF:

0.754

AC:

838454

AN:

1111802

Other (OTH)

AF:

0.735

AC:

44377

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

15166

30331

45497

60662

75828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20290

40580

60870

81160

101450

<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:

0.716

AC:

108959

AN:

152118

Hom.:

39499

Cov.:

AF XY:

0.720

AC XY:

53572

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.615

AC:

25532

AN:

41492

American (AMR)

AF:

0.748

AC:

11452

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.671

AC:

2331

AN:

3472

East Asian (EAS)

AF:

0.664

AC:

3419

AN:

5152

South Asian (SAS)

AF:

0.757

AC:

3647

AN:

4820

European-Finnish (FIN)

AF:

0.839

AC:

8892

AN:

10600

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.754

AC:

51267

AN:

67962

Other (OTH)

AF:

0.702

AC:

1485

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1542

3085

4627

6170

7712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.733

Hom.:

142625

Bravo

AF:

0.703

TwinsUK

AF:

0.762

AC:

2827

ALSPAC

AF:

0.746

AC:

2876

ESP6500AA

AF:

0.622

AC:

2739

ESP6500EA

AF:

0.748

AC:

6433

ExAC

AF:

0.737

AC:

89458

Asia WGS

AF:

0.741

AC:

2579

AN:

3478

EpiCase

AF:

0.736

EpiControl

AF:

0.737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.076

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.071

T;.;T;.;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.46

T;T;T;T;T

MetaRNN

Benign

8.8e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

N;.;.;.;.

PhyloP100

-0.74

PrimateAI

Benign

0.37

PROVEAN

Benign

0.83

N;.;N;N;N

REVEL

Benign

0.28

Sift

Benign

1.0

T;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;.;.;.;.

Vest4

0.095

MPC

0.089

ClinPred

0.0035

GERP RS

-4.2

PromoterAI

0.0091

Neutral

(source)

Varity_R

0.039

gMVP

0.26

Mutation Taster

=99/1

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over