Variant rs2289433 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

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

BP6

Variant 4-47837912-C-T is Benign according to our data. Variant chr4-47837912-C-T is described in Lovd as [Likely_benign].

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/exons	MANE	UniProt
CORIN	NM_006587.4 linkuse as main transcript	c.38G>A	p.Cys13Tyr	missense_variant	1/22	ENST00000273857.9
LOC101927179	NR_125880.1 linkuse as main transcript	n.164+6404C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORIN	ENST00000273857.9 linkuse as main transcript	c.38G>A	p.Cys13Tyr	missense_variant	1/22	1	NM_006587.4	P2	Q9Y5Q5-1
	ENST00000690605.1 linkuse as main transcript	n.176+6404C>T		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.738

AC:

185245

AN:

250996

Hom.:

68951

AF XY:

0.739

AC XY:

100325

AN XY:

135694

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 SAS exome

AF:

0.761

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

Gnomad4 AFR exome

AF:

0.603

Gnomad4 AMR exome

AF:

0.749

Gnomad4 ASJ exome

AF:

0.665

Gnomad4 EAS exome

AF:

0.646

Gnomad4 SAS exome

AF:

0.759

Gnomad4 FIN exome

AF:

0.831

Gnomad4 NFE exome

AF:

0.754

Gnomad4 OTH exome

AF:

0.735

GnomAD4 genome

AF:

0.716

AC:

108959

AN:

152118

Hom.:

39499

Cov.:

AF XY:

0.720

AC XY:

53572

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.615

Gnomad4 AMR

AF:

0.748

Gnomad4 ASJ

AF:

0.671

Gnomad4 EAS

AF:

0.664

Gnomad4 SAS

AF:

0.757

Gnomad4 FIN

AF:

0.839

Gnomad4 NFE

AF:

0.754

Gnomad4 OTH

AF:

0.702

Alfa

AF:

0.735

Hom.:

64936

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

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;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

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

Varity_R

0.039

gMVP

0.26

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over