rs75770792

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006587.4(CORIN):c.1664C>T(p.Thr555Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,613,568 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 93 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 75 hom. )

Consequence

CORIN
NM_006587.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.25

Publications

39 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007813364).

BP6

Variant 4-47661782-G-A is Benign according to our data. Variant chr4-47661782-G-A is described in ClinVar as Benign. ClinVar VariationId is 785091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006587.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CORIN	NM_006587.4	MANE Select	c.1664C>T	p.Thr555Ile	missense	Exon 12 of 22	NP_006578.2
CORIN	NM_001278585.2		c.1352C>T	p.Thr451Ile	missense	Exon 10 of 20	NP_001265514.1
CORIN	NM_001278586.2		c.1553C>T	p.Thr518Ile	missense	Exon 11 of 14	NP_001265515.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CORIN	ENST00000273857.9	TSL:1 MANE Select	c.1664C>T	p.Thr555Ile	missense	Exon 12 of 22	ENSP00000273857.4
CORIN	ENST00000505909.5	TSL:5	c.1553C>T	p.Thr518Ile	missense	Exon 11 of 21	ENSP00000425401.1
CORIN	ENST00000502252.5	TSL:2	c.1463C>T	p.Thr488Ile	missense	Exon 11 of 21	ENSP00000424212.1

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2797

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0640

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00456

AC:

1144

AN:

250680

AF XY:

0.00337

show subpopulations

Gnomad AFR exome

AF:

0.0622

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00176

AC:

2579

AN:

1461256

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1075

AN XY:

726916

show subpopulations

African (AFR)

AF:

0.0636

AC:

2128

AN:

33456

American (AMR)

AF:

0.00316

AC:

141

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.000290

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000351

AC:

AN:

1111656

Other (OTH)

AF:

0.00386

AC:

233

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

115

230

346

461

576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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:

0.0184

AC:

2799

AN:

152312

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1351

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0639

AC:

2655

AN:

41566

American (AMR)

AF:

0.00641

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68024

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

135

269

404

538

673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00596

Hom.:

Bravo

AF:

0.0206

ESP6500AA

AF:

0.0626

AC:

276

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00572

AC:

695

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.2

PhyloP100

7.3

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.40

Sift

Benign

0.12

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.68

MVP

0.92

MPC

0.34

ClinPred

0.030

GERP RS

5.0

Varity_R

0.20

gMVP

0.47

Mutation Taster

=82/18

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over