rs17462783

Positions:

• chr4-47641846-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.2198+74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 1,551,960 control chromosomes in the GnomAD database, including 5,790 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 0.088 (672 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5118 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]

LOC105374444 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORIN	NM_006587.4	c.2198+74A>G		intron_variant		ENST00000273857.9	NP_006578.2
LOC105374444	XR_007058109.1	n.2936-2140T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.2198+74A>G		intron_variant		1	NM_006587.4	ENSP00000273857	P2

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13445 AN: 152122 Hom.: 669 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.0740

GnomAD4 exome AF: 0.0817 AC: 114313 AN: 1399720 Hom.: 5118 AF XY: 0.0806 AC XY: 55917 AN XY: 693448

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.0375

Gnomad4 ASJ exome AF: 0.0591

Gnomad4 EAS exome AF: 0.00223

Gnomad4 SAS exome AF: 0.0362

Gnomad4 FIN exome AF: 0.0601

Gnomad4 NFE exome AF: 0.0900

Gnomad4 OTH exome AF: 0.0741

GnomAD4 genome AF: 0.0884 AC: 13459 AN: 152240 Hom.: 672 Cov.: 33 AF XY: 0.0847 AC XY: 6307 AN XY: 74442

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0298

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.0865

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0892 Hom.: 93

Bravo AF: 0.0893

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.0
DANN	Benign	0.65

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: rs17462783; hg19: chr4-47643863; COSMIC: COSV56697798; COSMIC: COSV56697798;