4-47786713-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High AC in GnomAd4 at 292 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4	c.409+12G>A		intron_variant	Intron 3 of 21	ENST00000273857.9	NP_006578.2
CORIN	NM_001278585.2	c.208+20190G>A		intron_variant	Intron 2 of 19		NP_001265514.1
CORIN	NM_001278586.2	c.409+12G>A		intron_variant	Intron 3 of 13		NP_001265515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.409+12G>A		intron_variant	Intron 3 of 21	1	NM_006587.4	ENSP00000273857.4

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

GnomAD3 exomes AF: 0.00202 AC: 508 AN: 251238 Hom.: 0 AF XY: 0.00190 AC XY: 258 AN XY: 135778

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.000569

Gnomad4 AMR exome AF: 0.00255

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000730

Gnomad4 NFE exome AF: 0.00346

Gnomad4 OTH exome AF: 0.00229

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

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00326

Gnomad4 OTH AF: 0.00237

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs61764288; hg19: chr4-47788730;