NM_006587.4:c.2199-7048T>G

Variant names:

• chr4-47633569-A-C
• rs4694863
• NM_006587.4:c.2199-7048T>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.2199-7048T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,080 control chromosomes in the GnomAD database, including 5,422 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 0.26 (5422 hom., cov: 33)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 3 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)

LOC105374444 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	NM_006587.4	MANE Select	c.2199-7048T>G		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.1887-7048T>G		intron	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.2199-7048T>G		intron	N/A	ENSP00000273857.4	Q9Y5Q5-1
	CORIN	ENST00000961995.1		c.2199-7048T>G		intron	N/A	ENSP00000632054.1
	CORIN	ENST00000961980.1		c.2181-7048T>G		intron	N/A	ENSP00000632039.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39717 AN: 151964 Hom.: 5412 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.261 AC: 39748 AN: 152080 Hom.: 5422 Cov.: 33 AF XY: 0.265 AC XY: 19673 AN XY: 74328

African (AFR) AF: 0.215 AC: 8904 AN: 41508

American (AMR) AF: 0.356 AC: 5446 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3472

East Asian (EAS) AF: 0.113 AC: 585 AN: 5182

South Asian (SAS) AF: 0.202 AC: 973 AN: 4822

European-Finnish (FIN) AF: 0.358 AC: 3766 AN: 10518

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.273 AC: 18535 AN: 67980

Other (OTH) AF: 0.252 AC: 533 AN: 2116

Alfa AF: 0.246 Hom.: 2460

Bravo AF: 0.261

Asia WGS AF: 0.175 AC: 611 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-1.0
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: rs4694863; hg19: chr4-47635586;