rs2289433

chr4-47837912-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_006587.4(CORIN):c.38G>A(p.Cys13Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,613,360 control chromosomes in the GnomAD database, including 449,782 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.72 (39499 hom., cov: 32)
  • Exomes 𝑓: 0.75 (410283 hom.)
• Consequence: CORIN NM_006587.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.7607765E-7).
• BP6: Variant 4-47837912-C-T is Benign according to our data. Variant chr4-47837912-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORIN	NM_006587.4	c.38G>A	p.Cys13Tyr	missense_variant	1/22	ENST00000273857.9
LOC101927179	NR_125880.1	n.164+6404C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORIN	ENST00000273857.9	c.38G>A	p.Cys13Tyr	missense_variant	1/22	1	NM_006587.4	P2
	ENST00000690605.1	n.176+6404C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108861 AN: 152000 Hom.: 39464 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.700

GnomAD3 exomes AF: 0.738 AC: 185245 AN: 250996 Hom.: 68951 AF XY: 0.739 AC XY: 100325 AN XY: 135694

Gnomad AFR exome AF: 0.617

Gnomad AMR exome AF: 0.751

Gnomad ASJ exome AF: 0.664

Gnomad EAS exome AF: 0.631

Gnomad SAS exome AF: 0.761

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.743

GnomAD4 exome AF: 0.748 AC: 1093049 AN: 1461242 Hom.: 410283 Cov.: 49 AF XY: 0.748 AC XY: 543700 AN XY: 726950

Gnomad4 AFR exome AF: 0.603

Gnomad4 AMR exome AF: 0.749

Gnomad4 ASJ exome AF: 0.665

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.759

Gnomad4 FIN exome AF: 0.831

Gnomad4 NFE exome AF: 0.754

Gnomad4 OTH exome AF: 0.735

GnomAD4 genome AF: 0.716 AC: 108959 AN: 152118 Hom.: 39499 Cov.: 32 AF XY: 0.720 AC XY: 53572 AN XY: 74368

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.839

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.702

Alfa AF: 0.735 Hom.: 64936

Bravo AF: 0.703

TwinsUK AF: 0.762 AC: 2827

ALSPAC AF: 0.746 AC: 2876

ESP6500AA AF: 0.622 AC: 2739

ESP6500EA AF: 0.748 AC: 6433

ExAC AF: 0.737 AC: 89458

Asia WGS AF: 0.741 AC: 2579 AN: 3478

EpiCase AF: 0.736

EpiControl AF: 0.737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	0.076
Dann	Benign	0.80
DEOGEN2	Benign	0.071	T;.;T;.;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.46	T;T;T;T;T
MetaRNN	Benign	8.8e-7	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.83	N;.;N;N;N
REVEL	Benign	0.28
Sift	Benign	1.0	T;.;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;.;.;.;.
Vest4		0.095
MPC		0.089
ClinPred		0.0035	T
GERP RS		-4.2
Varity_R		0.039
gMVP		0.26

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: rs2289433; hg19: chr4-47839929; COSMIC: COSV56692138; COSMIC: COSV56692138;