4-47624017-C-T

Variant names:

• chr4-47624017-C-T
• rs1344122
• NM_006587.4:c.2316-69G>A

Variant summary

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

The NM_006587.4(CORIN):​c.2316-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,296,434 control chromosomes in the GnomAD database, including 47,557 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 0.27 (5657 hom., cov: 32)
  • Exomes 𝑓: 0.27 (41900 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

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]

LOC105374444 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4	c.2316-69G>A		intron_variant	Intron 17 of 21	ENST00000273857.9	NP_006578.2
CORIN	NM_001278585.2	c.2004-69G>A		intron_variant	Intron 15 of 19		NP_001265514.1
LOC105374444	XR_007058109.1	n.87+246C>T		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.2316-69G>A		intron_variant	Intron 17 of 21	1	NM_006587.4	ENSP00000273857.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40906 AN: 151966 Hom.: 5648 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.265 AC: 303572 AN: 1144348 Hom.: 41900 AF XY: 0.262 AC XY: 153007 AN XY: 583950

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.269 AC: 40934 AN: 152086 Hom.: 5657 Cov.: 32 AF XY: 0.272 AC XY: 20204 AN XY: 74350

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.257

Alfa AF: 0.265 Hom.: 850

Bravo AF: 0.269

Asia WGS AF: 0.175 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.67

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: rs1344122; hg19: chr4-47626034; COSMIC: COSV56692236;