Variant rs55932196 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001278586.2(CORIN):c.2059C>T(p.His687Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00981 in 1,578,336 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0089 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0099 ( 96 hom. )

Consequence

CORIN
NM_001278586.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.70

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 links:

CORIN (HGNC:):

CORIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004630983).

BP6

Variant 4-47643044-G-A is Benign according to our data. Variant chr4-47643044-G-A is described in ClinVar as [Benign]. Clinvar id is 1695093.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORIN	NM_006587.4 linkuse as main transcript	c.2068+102C>T		intron_variant		ENST00000273857.9	NP_006578.2	Q9Y5Q5-1B4E2W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9 linkuse as main transcript	c.2068+102C>T		intron_variant		1	NM_006587.4	ENSP00000273857.4		Q9Y5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.00894

AC:

1361

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0207

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00926

AC:

1823

AN:

196824

Hom.:

AF XY:

0.00907

AC XY:

958

AN XY:

105654

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.00513

Gnomad ASJ exome

AF:

0.00917

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00214

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00990

AC:

14119

AN:

1426040

Hom.:

Cov.:

AF XY:

0.00966

AC XY:

6824

AN XY:

706692

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00512

Gnomad4 ASJ exome

AF:

0.00829

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00272

Gnomad4 FIN exome

AF:

0.0224

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00783

GnomAD4 genome

AF:

0.00892

AC:

1359

AN:

152296

Hom.:

Cov.:

AF XY:

0.00926

AC XY:

690

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00229

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0207

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00923

Hom.:

Bravo

AF:

0.00754

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00882

AC:

ExAC

AF:

0.00944

AC:

1137

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CORIN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 03, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

CORIN: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.47

DEOGEN2

Benign

0.23

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.75

PROVEAN

Benign

-0.48

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Vest4

0.097

MVP

0.63

ClinPred

0.078

GERP RS

2.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over