rs74503412

chr4-47653507-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006587.4(CORIN):c.1843+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,433,538 control chromosomes in the GnomAD database, including 438 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 0.031 (231 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (207 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORIN	NM_006587.4	c.1843+46A>G		intron_variant		ENST00000273857.9
CORIN	NM_001278585.2	c.1531+46A>G		intron_variant
CORIN	NM_001278586.2	c.1732+46A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORIN	ENST00000273857.9	c.1843+46A>G		intron_variant		1	NM_006587.4	P2

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4673 AN: 152202 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00813 AC: 1986 AN: 244386 Hom.: 117 AF XY: 0.00589 AC XY: 776 AN XY: 131844

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.00555

Gnomad ASJ exome AF: 0.000205

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000242

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000288

Gnomad OTH exome AF: 0.00387

GnomAD4 exome AF: 0.00318 AC: 4072 AN: 1281218 Hom.: 207 Cov.: 18 AF XY: 0.00277 AC XY: 1793 AN XY: 646128

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.00623

Gnomad4 ASJ exome AF: 0.0000805

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000210

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000169

Gnomad4 OTH exome AF: 0.00697

GnomAD4 genome AF: 0.0307 AC: 4679 AN: 152320 Hom.: 231 Cov.: 32 AF XY: 0.0297 AC XY: 2216 AN XY: 74492

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.00987

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0164 Hom.: 18

Bravo AF: 0.0341

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.9
Dann	Benign	0.60

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: rs74503412; hg19: chr4-47655524;