rs61759692

Positions:

• chr4-47645035-G-A
• chr4-47645035-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006587.4(CORIN):​c.1957+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,101,792 control chromosomes in the GnomAD database, including 488 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 0.022 (48 hom., cov: 32)
  • Exomes 𝑓: 0.027 (440 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0216 (3283/152246) while in subpopulation NFE AF= 0.033 (2241/68006). AF 95% confidence interval is 0.0318. There are 48 homozygotes in gnomad4. There are 1549 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3283 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORIN	NM_006587.4	c.1957+46C>T		intron_variant		ENST00000273857.9	NP_006578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.1957+46C>T		intron_variant		1	NM_006587.4	ENSP00000273857.4

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3282 AN: 152126 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.00570

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.0212 AC: 4768 AN: 225128 Hom.: 74 AF XY: 0.0216 AC XY: 2630 AN XY: 121660

Gnomad AFR exome AF: 0.00532

Gnomad AMR exome AF: 0.00596

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00624

Gnomad FIN exome AF: 0.0370

Gnomad NFE exome AF: 0.0320

Gnomad OTH exome AF: 0.0195

GnomAD4 exome AF: 0.0272 AC: 25847 AN: 949546 Hom.: 440 Cov.: 12 AF XY: 0.0266 AC XY: 13053 AN XY: 490916

Gnomad4 AFR exome AF: 0.00492

Gnomad4 AMR exome AF: 0.00668

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00576

Gnomad4 FIN exome AF: 0.0352

Gnomad4 NFE exome AF: 0.0331

Gnomad4 OTH exome AF: 0.0244

GnomAD4 genome AF: 0.0216 AC: 3283 AN: 152246 Hom.: 48 Cov.: 32 AF XY: 0.0208 AC XY: 1549 AN XY: 74444

Gnomad4 AFR AF: 0.00568

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00727

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0330

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0216 Hom.: 21

Bravo AF: 0.0182

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.42
DANN	Benign	0.44

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: rs61759692; hg19: chr4-47647052;