Genetic Variant NM_006587.4:c.1843+46A>G (chr4-47653507-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006587.4(CORIN):c.1843+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,433,538 control chromosomes in the GnomAD database, including 438 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 0.031 ( 231 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 207 hom. )

Consequence

CORIN
NM_006587.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.446

Publications

2 publications found

Variant links:

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]

CORIN Gene-Disease associations (from GenCC):

preeclampsia/eclampsia 5
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CORIN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4 link	c.1843+46A>G	intron_variant	Intron 13 of 21	ENST00000273857.9	NP_006578.2	Q9Y5Q5-1B4E2W9
CORIN	NM_001278585.2 link	c.1531+46A>G	intron_variant	Intron 11 of 19		NP_001265514.1	Q9Y5Q5A0A087X1D5B4E1Y7B4E2W9
CORIN	NM_001278586.2 link	c.1732+46A>G	intron_variant	Intron 12 of 13		NP_001265515.1	J3KR83B4E2W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9 link	c.1843+46A>G		intron_variant	Intron 13 of 21	1	NM_006587.4	ENSP00000273857.4		Q9Y5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4673

AN:

152202

Hom.:

231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00988

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.00813

AC:

1986

AN:

244386

AF XY:

0.00589

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.00555

Gnomad ASJ exome

AF:

0.000205

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000288

Gnomad OTH exome

AF:

0.00387

GnomAD4 exome

AF:

0.00318

AC:

4072

AN:

1281218

Hom.:

207

Cov.:

AF XY:

0.00277

AC XY:

1793

AN XY:

646128

show subpopulations

African (AFR)

AF:

0.108

AC:

3202

AN:

29620

American (AMR)

AF:

0.00623

AC:

269

AN:

43200

Ashkenazi Jewish (ASJ)

AF:

0.0000805

AC:

AN:

24856

East Asian (EAS)

AF:

0.00

AC:

AN:

38710

South Asian (SAS)

AF:

0.000210

AC:

AN:

81142

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53210

Middle Eastern (MID)

AF:

0.00777

AC:

AN:

5402

European-Non Finnish (NFE)

AF:

0.000169

AC:

161

AN:

950880

Other (OTH)

AF:

0.00697

AC:

378

AN:

54198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

185

370

556

741

926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0307

AC:

4679

AN:

152320

Hom.:

231

Cov.:

AF XY:

0.0297

AC XY:

2216

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.107

AC:

4462

AN:

41558

American (AMR)

AF:

0.00987

AC:

151

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000367

AC:

AN:

68032

Other (OTH)

AF:

0.0166

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

211

422

634

845

1056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0341

Asia WGS

AF:

0.00837

AC:

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

1.9

(source)

DANN

Benign

0.60

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over