Genetic Variant NM_006587.4:c.1133-14A>C (chr4-47678068-T-G) – 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.1133-14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,541,140 control chromosomes in the GnomAD database, including 69,017 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 0.37 ( 13247 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55770 hom. )

Consequence

CORIN
NM_006587.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.109

Publications

18 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006587.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CORIN	NM_006587.4	MANE Select	c.1133-14A>C	intron	N/A	NP_006578.2
CORIN	NM_001278585.2		c.821-14A>C	intron	N/A	NP_001265514.1	A0A087X1D5
CORIN	NM_001278586.2		c.1022-14A>C	intron	N/A	NP_001265515.1	J3KR83

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CORIN	ENST00000273857.9	TSL:1 MANE Select	c.1133-14A>C	intron	N/A	ENSP00000273857.4	Q9Y5Q5-1
CORIN	ENST00000961995.1		c.1133-14A>C	intron	N/A	ENSP00000632054.1
CORIN	ENST00000961980.1		c.1115-14A>C	intron	N/A	ENSP00000632039.1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56387

AN:

151948

Hom.:

13211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.337

GnomAD2 exomes

AF:

0.305

AC:

76319

AN:

250388

AF XY:

0.289

show subpopulations

Gnomad AFR exome

AF:

0.668

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.629

Gnomad FIN exome

AF:

0.275

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.267

AC:

371010

AN:

1389072

Hom.:

55770

Cov.:

AF XY:

0.263

AC XY:

182919

AN XY:

695508

show subpopulations

African (AFR)

AF:

0.674

AC:

21589

AN:

32044

American (AMR)

AF:

0.309

AC:

13768

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

4286

AN:

25632

East Asian (EAS)

AF:

0.618

AC:

24302

AN:

39332

South Asian (SAS)

AF:

0.209

AC:

17692

AN:

84688

European-Finnish (FIN)

AF:

0.270

AC:

14391

AN:

53378

Middle Eastern (MID)

AF:

0.217

AC:

1219

AN:

5626

European-Non Finnish (NFE)

AF:

0.246

AC:

257056

AN:

1045774

Other (OTH)

AF:

0.288

AC:

16707

AN:

57982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

12715

25431

38146

50862

63577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8812

17624

26436

35248

44060

<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:

0.371

AC:

56478

AN:

152068

Hom.:

13247

Cov.:

AF XY:

0.367

AC XY:

27272

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.652

AC:

27049

AN:

41464

American (AMR)

AF:

0.286

AC:

4367

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

570

AN:

3468

East Asian (EAS)

AF:

0.621

AC:

3207

AN:

5164

South Asian (SAS)

AF:

0.207

AC:

999

AN:

4824

European-Finnish (FIN)

AF:

0.271

AC:

2868

AN:

10580

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.243

AC:

16551

AN:

67984

Other (OTH)

AF:

0.341

AC:

718

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1549

3097

4646

6194

7743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.297

Hom.:

3332

Bravo

AF:

0.391

Asia WGS

AF:

0.434

AC:

1507

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.1

(source)

DANN

Benign

0.39

PhyloP100

0.11

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over