rs3805392

chr4-47653713-A-G

Variant summary

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

The NM_006587.4(CORIN):c.1736-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,446,900 control chromosomes in the GnomAD database, including 12,033 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 0.094 (1224 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10809 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORIN	NM_006587.4	c.1736-53T>C		intron_variant		ENST00000273857.9
CORIN	NM_001278585.2	c.1424-53T>C		intron_variant
CORIN	NM_001278586.2	c.1625-53T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORIN	ENST00000273857.9	c.1736-53T>C		intron_variant		1	NM_006587.4	P2

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14337 AN: 152084 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.108 AC: 139348 AN: 1294698 Hom.: 10809 AF XY: 0.108 AC XY: 70151 AN XY: 651316

Gnomad4 AFR exome AF: 0.0247

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.0918

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0900

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0942 AC: 14344 AN: 152202 Hom.: 1224 Cov.: 32 AF XY: 0.0971 AC XY: 7223 AN XY: 74416

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0909

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0856 Hom.: 81

Bravo AF: 0.0974

Asia WGS AF: 0.257 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.13
Dann	Benign	0.38

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: rs3805392; hg19: chr4-47655730; COSMIC: COSV56686467; COSMIC: COSV56686467;