rs10517195

Positions:

• chr4-47680157-A-G
• chr4-47680157-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_006587.4(CORIN):​c.1116T>C​(p.Ser372=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,611,108 control chromosomes in the GnomAD database, including 256,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.47 (18592 hom., cov: 32)
  • Exomes 𝑓: 0.56 (237453 hom.)
• Consequence: CORIN NM_006587.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-47680157-A-G is Benign according to our data. Variant chr4-47680157-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.919 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORIN	NM_006587.4	c.1116T>C	p.Ser372=	synonymous_variant	8/22	ENST00000273857.9	NP_006578.2
CORIN	NM_001278585.2	c.821-2103T>C		intron_variant			NP_001265514.1
CORIN	NM_001278586.2	c.1022-2103T>C		intron_variant			NP_001265515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.1116T>C	p.Ser372=	synonymous_variant	8/22	1	NM_006587.4	ENSP00000273857	P2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72187 AN: 152034 Hom.: 18580 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.483

GnomAD3 exomes AF: 0.503 AC: 125722 AN: 250138 Hom.: 33880 AF XY: 0.509 AC XY: 68873 AN XY: 135192

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.474

Gnomad FIN exome AF: 0.554

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.523

GnomAD4 exome AF: 0.562 AC: 820435 AN: 1458956 Hom.: 237453 Cov.: 32 AF XY: 0.561 AC XY: 407097 AN XY: 725964

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.528

GnomAD4 genome AF: 0.475 AC: 72223 AN: 152152 Hom.: 18592 Cov.: 32 AF XY: 0.470 AC XY: 34997 AN XY: 74402

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.478

Alfa AF: 0.558 Hom.: 49433

Bravo AF: 0.461

Asia WGS AF: 0.326 AC: 1134 AN: 3478

EpiCase AF: 0.583

EpiControl AF: 0.574

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.57
DANN	Benign	0.55

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: rs10517195; hg19: chr4-47682174; COSMIC: COSV56698906;