chr4-47678068-T-G

Position:

• chr4-47678068-T-G

Variant summary

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

The NM_006587.4(CORIN):​c.1133-14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,541,140 control chromosomes in the GnomAD database, including 69,017 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 0.37 (13247 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55770 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORIN	NM_006587.4	c.1133-14A>C		intron_variant		ENST00000273857.9	NP_006578.2
CORIN	NM_001278585.2	c.821-14A>C		intron_variant			NP_001265514.1
CORIN	NM_001278586.2	c.1022-14A>C		intron_variant			NP_001265515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.1133-14A>C		intron_variant		1	NM_006587.4	ENSP00000273857.4

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56387 AN: 151948 Hom.: 13211 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.337

GnomAD3 exomes AF: 0.305 AC: 76319 AN: 250388 Hom.: 14292 AF XY: 0.289 AC XY: 39073 AN XY: 135264

Gnomad AFR exome AF: 0.668

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.629

Gnomad SAS exome AF: 0.207

Gnomad FIN exome AF: 0.275

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.267 AC: 371010 AN: 1389072 Hom.: 55770 Cov.: 23 AF XY: 0.263 AC XY: 182919 AN XY: 695508

Gnomad4 AFR exome AF: 0.674

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.618

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.371 AC: 56478 AN: 152068 Hom.: 13247 Cov.: 32 AF XY: 0.367 AC XY: 27272 AN XY: 74316

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.341

Alfa AF: 0.299 Hom.: 2227

Bravo AF: 0.391

Asia WGS AF: 0.434 AC: 1507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.39

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: rs2271037; hg19: chr4-47680085;