chr4-47595892-ACC-TCT

Variant names:

• chr4-47595892-ACC-TCT
• NM_006587.4:c.2956_2958delGGTinsAGA
• CORIN p.Gly986Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_006587.4(CORIN):​c.2956_2958delGGTinsAGA​(p.Gly986Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G986C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CORIN NM_006587.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.70
• Publications: 0 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	NM_006587.4	MANE Select	c.2956_2958delGGTinsAGA	p.Gly986Arg	missense	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.2644_2646delGGTinsAGA	p.Gly882Arg	missense	N/A	NP_001265514.1	A0A087X1D5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.2956_2958delGGTinsAGA	p.Gly986Arg	missense	N/A	ENSP00000273857.4	Q9Y5Q5-1
	CORIN	ENST00000961995.1		c.3031_3033delGGTinsAGA	p.Gly1011Arg	missense	N/A	ENSP00000632054.1
	CORIN	ENST00000961980.1		c.2938_2940delGGTinsAGA	p.Gly980Arg	missense	N/A	ENSP00000632039.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-47597909;