rs6832495

Variant names:

• chr4-47607647-G-A
• rs6832495
• NM_006587.4:c.2541-3979C>T

Variant summary

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

The NM_006587.4(CORIN):​c.2541-3979C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,966 control chromosomes in the GnomAD database, including 31,262 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 0.63 (31262 hom., cov: 31)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 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.2541-3979C>T		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.2229-3979C>T		intron	N/A	NP_001265514.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.2541-3979C>T		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.2430-3979C>T		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.2340-3979C>T		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95716 AN: 151850 Hom.: 31221 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.631 AC: 95818 AN: 151966 Hom.: 31262 Cov.: 31 AF XY: 0.629 AC XY: 46742 AN XY: 74270

African (AFR) AF: 0.787 AC: 32639 AN: 41454

American (AMR) AF: 0.649 AC: 9911 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1632 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3894 AN: 5158

South Asian (SAS) AF: 0.461 AC: 2218 AN: 4808

European-Finnish (FIN) AF: 0.626 AC: 6605 AN: 10550

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37233 AN: 67942

Other (OTH) AF: 0.608 AC: 1281 AN: 2108

Alfa AF: 0.574 Hom.: 81713

Bravo AF: 0.644

Asia WGS AF: 0.614 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.1
DANN	Benign	0.57
PhyloP100		0.32
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: rs6832495; hg19: chr4-47609664;