4-47665207-T-C

Variant names:

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

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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.1414A>G	p.Ser472Gly	missense	Exon 11 of 22	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.1303A>G	p.Ser435Gly	missense	Exon 10 of 21	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.1213A>G	p.Ser405Gly	missense	Exon 10 of 21	ENSP00000424212.1

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

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.67
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N
REVEL	Pathogenic	0.71
Sift	Benign	0.34	T
Sift4G	Uncertain	0.030	D
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;