rs55932196

chr4-47643044-G-Achr4-47643044-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_006587.4(CORIN):c.2068+102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00981 in 1,578,336 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0099 (96 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.70

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004630983).
• BP6: Variant 4-47643044-G-A is Benign according to our data. Variant chr4-47643044-G-A is described in ClinVar as [Benign]. Clinvar id is 1695093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 1361 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORIN	NM_006587.4	c.2068+102C>T		intron_variant		ENST00000273857.9
LOC105374444	XR_007058109.1	n.2936-942G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORIN	ENST00000273857.9	c.2068+102C>T		intron_variant		1	NM_006587.4	P2

Frequencies

GnomAD3 genomes AF: 0.00894 AC: 1361 AN: 152178 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00926 AC: 1823 AN: 196824 Hom.: 10 AF XY: 0.00907 AC XY: 958 AN XY: 105654

Gnomad AFR exome AF: 0.00146

Gnomad AMR exome AF: 0.00513

Gnomad ASJ exome AF: 0.00917

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00214

Gnomad FIN exome AF: 0.0220

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.00990 AC: 14119 AN: 1426040 Hom.: 96 Cov.: 32 AF XY: 0.00966 AC XY: 6824 AN XY: 706692

Gnomad4 AFR exome AF: 0.00123

Gnomad4 AMR exome AF: 0.00512

Gnomad4 ASJ exome AF: 0.00829

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00272

Gnomad4 FIN exome AF: 0.0224

Gnomad4 NFE exome AF: 0.0109

Gnomad4 OTH exome AF: 0.00783

GnomAD4 genome AF: 0.00892 AC: 1359 AN: 152296 Hom.: 9 Cov.: 33 AF XY: 0.00926 AC XY: 690 AN XY: 74474

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0128

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.00923 Hom.: 0

Bravo AF: 0.00754

TwinsUK AF: 0.00917 AC: 34

ALSPAC AF: 0.00882 AC: 34

ExAC AF: 0.00944 AC: 1137

Asia WGS AF: 0.000578 AC: 2 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CORIN-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 03, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

CORIN: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	12
Dann	Benign	0.47
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.75	T
MutationTaster	Benign	1.0	N;N;N;N;N
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Vest4		0.097
MVP		0.63
ClinPred		0.078	T
GERP RS		2.7

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: rs55932196; hg19: chr4-47645061;