Variant 4-47683803-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The ENST00000273857.9(CORIN):c.949A>G(p.Lys317Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CORIN
ENST00000273857.9 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.87

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.854

PP5

Variant 4-47683803-T-C is Pathogenic according to our data. Variant chr4-47683803-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 30450.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CORIN	NM_006587.4 linkuse as main transcript	c.949A>G	p.Lys317Glu	missense_variant	7/22	ENST00000273857.9	NP_006578.2
CORIN	NM_001278585.2 linkuse as main transcript	c.748A>G	p.Lys250Glu	missense_variant	6/20		NP_001265514.1
CORIN	NM_001278586.2 linkuse as main transcript	c.949A>G	p.Lys317Glu	missense_variant	7/14		NP_001265515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9 linkuse as main transcript	c.949A>G	p.Lys317Glu	missense_variant	7/22	1	NM_006587.4	ENSP00000273857	P2	Q9Y5Q5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250622

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Preeclampsia/eclampsia 5

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 21, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.;.;T;.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

T;T;T;T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.85

D;D;D;D;D;D

MetaSVM

Pathogenic

0.83

MutationAssessor

Benign

0.70

N;.;.;.;.;.

MutationTaster

Benign

0.94

D;D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

N;.;N;N;N;N

REVEL

Pathogenic

0.83

Sift

Benign

0.10

T;.;T;T;T;T

Sift4G

Benign

0.075

T;T;T;T;T;T

Polyphen

1.0

D;.;.;.;.;.

Vest4

0.71

MutPred

0.54

Loss of methylation at K317 (P = 0.0032);.;.;.;Loss of methylation at K317 (P = 0.0032);Loss of methylation at K317 (P = 0.0032);

MVP

0.94

MPC

0.35

ClinPred

0.81

GERP RS

5.8

Varity_R

0.33

gMVP

0.81

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