chr4-47786713-C-T

Variant names:

• chr4-47786713-C-T
• rs61764288
• NM_006587.4:c.409+12G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006587.4(CORIN):​c.409+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,610,124 control chromosomes in the GnomAD database, including 10 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 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (9 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High Homozygotes in GnomAdExome4 at 9 Unknown gene

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.409+12G>A		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.208+20190G>A		intron	N/A	NP_001265514.1	A0A087X1D5
	CORIN	NM_001278586.2		c.409+12G>A		intron	N/A	NP_001265515.1	J3KR83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.409+12G>A		intron	N/A	ENSP00000273857.4	Q9Y5Q5-1
	CORIN	ENST00000961995.1		c.409+12G>A		intron	N/A	ENSP00000632054.1
	CORIN	ENST00000961980.1		c.409+12G>A		intron	N/A	ENSP00000632039.1

Frequencies

GnomAD3 genomes AF: 0.00192 AC: 292 AN: 152142 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00326

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00202 AC: 508 AN: 251238 AF XY: 0.00190

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000509

Gnomad NFE exome AF: 0.00339

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00285 AC: 4161 AN: 1457864 Hom.: 9 Cov.: 30 AF XY: 0.00267 AC XY: 1941 AN XY: 725608

African (AFR) AF: 0.000569 AC: 19 AN: 33390

American (AMR) AF: 0.00255 AC: 114 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86156

European-Finnish (FIN) AF: 0.000730 AC: 39 AN: 53414

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.00346 AC: 3840 AN: 1108360

Other (OTH) AF: 0.00229 AC: 138 AN: 60286

GnomAD4 genome AF: 0.00192 AC: 292 AN: 152260 Hom.: 1 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74446

African (AFR) AF: 0.000578 AC: 24 AN: 41556

American (AMR) AF: 0.00229 AC: 35 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00326 AC: 222 AN: 68014

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00291 Hom.: 0

Bravo AF: 0.00217

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.66
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism

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: rs61764288; hg19: chr4-47788730;