NM_006587.4:c.38G>A

Variant names:

• chr4-47837912-C-T
• rs2289433
• NM_006587.4:c.38G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (39499 hom., cov: 32)
  • Exomes 𝑓: 0.75 (410283 hom.)
• Consequence: CORIN NM_006587.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 41 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)

ENSG00000282917 (HGNC:58782):

LOC101927179 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.7607765E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

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.38G>A	p.Cys13Tyr	missense	Exon 1 of 22	NP_006578.2
	CORIN	NM_001278585.2		c.38G>A	p.Cys13Tyr	missense	Exon 1 of 20	NP_001265514.1
	CORIN	NM_001278586.2		c.38G>A	p.Cys13Tyr	missense	Exon 1 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.38G>A	p.Cys13Tyr	missense	Exon 1 of 22	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.38G>A	p.Cys13Tyr	missense	Exon 1 of 21	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.38G>A	p.Cys13Tyr	missense	Exon 1 of 21	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108861 AN: 152000 Hom.: 39464 Cov.: 32

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

GnomAD2 exomes AF: 0.738 AC: 185245 AN: 250996 AF XY: 0.739

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 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.: 49 AF XY: 0.748 AC XY: 543700 AN XY: 726950

African (AFR) AF: 0.603 AC: 20200 AN: 33474

American (AMR) AF: 0.749 AC: 33497 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 17368 AN: 26136

East Asian (EAS) AF: 0.646 AC: 25629 AN: 39694

South Asian (SAS) AF: 0.759 AC: 65435 AN: 86236

European-Finnish (FIN) AF: 0.831 AC: 44080 AN: 53074

Middle Eastern (MID) AF: 0.701 AC: 4009 AN: 5722

European-Non Finnish (NFE) AF: 0.754 AC: 838454 AN: 1111802

Other (OTH) AF: 0.735 AC: 44377 AN: 60384

GnomAD4 genome AF: 0.716 AC: 108959 AN: 152118 Hom.: 39499 Cov.: 32 AF XY: 0.720 AC XY: 53572 AN XY: 74368

African (AFR) AF: 0.615 AC: 25532 AN: 41492

American (AMR) AF: 0.748 AC: 11452 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2331 AN: 3472

East Asian (EAS) AF: 0.664 AC: 3419 AN: 5152

South Asian (SAS) AF: 0.757 AC: 3647 AN: 4820

European-Finnish (FIN) AF: 0.839 AC: 8892 AN: 10600

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51267 AN: 67962

Other (OTH) AF: 0.702 AC: 1485 AN: 2114

Alfa AF: 0.733 Hom.: 142625

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.076
DANN	Benign	0.80
DEOGEN2	Benign	0.071	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	8.8e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.74
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.28
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.095
MPC		0.089
ClinPred		0.0035	T
GERP RS		-4.2
PromoterAI		0.0091	Neutral
Varity_R		0.039
gMVP		0.26
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289433; hg19: chr4-47839929; COSMIC: COSV56692138; COSMIC: COSV56692138;