rs2351784

Variant names:

• chr4-47667418-T-C
• rs2351784
• NM_006587.4:c.1358-2155A>G

Variant summary

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

The NM_006587.4(CORIN):​c.1358-2155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,014 control chromosomes in the GnomAD database, including 22,614 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22614 hom., cov: 32)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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.1358-2155A>G		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.1046-2155A>G		intron	N/A	NP_001265514.1
	CORIN	NM_001278586.2		c.1247-2155A>G		intron	N/A	NP_001265515.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.1358-2155A>G		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.1247-2155A>G		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.1157-2155A>G		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80771 AN: 151896 Hom.: 22581 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.532 AC: 80867 AN: 152014 Hom.: 22614 Cov.: 32 AF XY: 0.534 AC XY: 39675 AN XY: 74290

African (AFR) AF: 0.671 AC: 27812 AN: 41468

American (AMR) AF: 0.579 AC: 8850 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1248 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3903 AN: 5164

South Asian (SAS) AF: 0.395 AC: 1900 AN: 4812

European-Finnish (FIN) AF: 0.557 AC: 5883 AN: 10558

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29860 AN: 67958

Other (OTH) AF: 0.507 AC: 1069 AN: 2108

Alfa AF: 0.455 Hom.: 8373

Bravo AF: 0.546

Asia WGS AF: 0.568 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.32
PhyloP100		-0.89
Mutation Taster		=100/0	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: rs2351784; hg19: chr4-47669435;