rs387906895

Variant names:

• chr4-47665207-T-C
• rs387906895
• NM_006587.4:c.1414A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-47665207-T-C
• chr4-47665207-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_006587.4(CORIN):​c.1414A>G​(p.Ser472Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CORIN NM_006587.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.666
• Publications: 15 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-47665207-T-C is Pathogenic according to our data. Variant chr4-47665207-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 30451.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4	c.1414A>G	p.Ser472Gly	missense_variant	Exon 11 of 22	ENST00000273857.9	NP_006578.2
CORIN	NM_001278585.2	c.1102A>G	p.Ser368Gly	missense_variant	Exon 9 of 20		NP_001265514.1
CORIN	NM_001278586.2	c.1303A>G	p.Ser435Gly	missense_variant	Exon 10 of 14		NP_001265515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.1414A>G	p.Ser472Gly	missense_variant	Exon 11 of 22	1	NM_006587.4	ENSP00000273857.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Preeclampsia/eclampsia 5 Pathogenic:1

Mar 21, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.7
DANN	Benign	0.86
DEOGEN2	Benign	0.20	T;.;.;T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.85	D;D;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L;.;.;.;.;.
PhyloP100		0.67
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N;.;N;N;N;N
REVEL	Pathogenic	0.71
Sift	Benign	0.34	T;.;T;T;T;T
Sift4G	Uncertain	0.030	D;D;D;D;D;T
Polyphen		0.24	B;.;.;.;.;.
Vest4		0.17
MutPred		0.57		Gain of glycosylation at Y476 (P = 0.0466);.;.;.;.;.;
MVP		0.67
MPC		0.053
ClinPred		0.60	D
GERP RS		-6.5
Varity_R		0.079
gMVP		0.43
Mutation Taster		=7/93	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs387906895; hg19: chr4-47667224;