dbSNP rs61759670: CORIN:p.Tyr907Tyr (chr4-47603488-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006587.4(CORIN):c.2721C>T(p.Tyr907Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 1,614,098 control chromosomes in the GnomAD database, including 729 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 0.018 ( 54 hom., cov: 32)

Exomes 𝑓: 0.021 ( 675 hom. )

Consequence

CORIN
NM_006587.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.229

Publications

6 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-0.229 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4 link	c.2721C>T	p.Tyr907Tyr	synonymous_variant	Exon 20 of 22	ENST00000273857.9	NP_006578.2	Q9Y5Q5-1B4E2W9
CORIN	NM_001278585.2 link	c.2409C>T	p.Tyr803Tyr	synonymous_variant	Exon 18 of 20		NP_001265514.1	Q9Y5Q5A0A087X1D5B4E1Y7B4E2W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9 link	c.2721C>T	p.Tyr907Tyr	synonymous_variant	Exon 20 of 22	1	NM_006587.4	ENSP00000273857.4		Q9Y5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

2705

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00314

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0267

Gnomad ASJ

AF:

0.0613

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0774

Gnomad FIN

AF:

0.00839

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0271

AC:

6803

AN:

250982

AF XY:

0.0311

show subpopulations

Gnomad AFR exome

AF:

0.00296

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0555

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.0218

Gnomad OTH exome

AF:

0.0307

GnomAD4 exome

AF:

0.0212

AC:

30940

AN:

1461824

Hom.:

675

Cov.:

AF XY:

0.0235

AC XY:

17085

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00344

AC:

115

AN:

33478

American (AMR)

AF:

0.0190

AC:

849

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0541

AC:

1413

AN:

26134

East Asian (EAS)

AF:

0.000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0825

AC:

7119

AN:

86258

European-Finnish (FIN)

AF:

0.0108

AC:

579

AN:

53386

Middle Eastern (MID)

AF:

0.0836

AC:

482

AN:

5768

European-Non Finnish (NFE)

AF:

0.0169

AC:

18821

AN:

1111996

Other (OTH)

AF:

0.0257

AC:

1552

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1918

3835

5753

7670

9588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.0177

AC:

2700

AN:

152274

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1378

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00313

AC:

130

AN:

41568

American (AMR)

AF:

0.0267

AC:

408

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0613

AC:

213

AN:

3472

East Asian (EAS)

AF:

0.000966

AC:

AN:

5178

South Asian (SAS)

AF:

0.0772

AC:

372

AN:

4818

European-Finnish (FIN)

AF:

0.00839

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0203

AC:

1382

AN:

68018

Other (OTH)

AF:

0.0284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

134

268

402

536

670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0177

Hom.:

Bravo

AF:

0.0167

EpiCase

AF:

0.0273

EpiControl

AF:

0.0277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.27

(source)

DANN

Benign

0.31

PhyloP100

-0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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