Genetic Variant NM_006587.4:c.2199-7048T>G (chr4-47633569-A-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.2199-7048T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,080 control chromosomes in the GnomAD database, including 5,422 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 0.26 ( 5422 hom., cov: 33)

Consequence

CORIN
NM_006587.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

3 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:

LOC105374444 (HGNC:):

LOC105374444 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=-0.99).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4 link	c.2199-7048T>G	intron_variant	Intron 16 of 21	ENST00000273857.9	NP_006578.2	Q9Y5Q5-1B4E2W9
CORIN	NM_001278585.2 link	c.1887-7048T>G	intron_variant	Intron 14 of 19		NP_001265514.1	Q9Y5Q5A0A087X1D5B4E1Y7B4E2W9
LOC105374444	XR_007058109.1 link	n.384+2004A>C	intron_variant	Intron 4 of 5
LOC105374444	XR_925284.3 link	n.591+2004A>C	intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9 link	c.2199-7048T>G		intron_variant	Intron 16 of 21	1	NM_006587.4	ENSP00000273857.4		Q9Y5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39717

AN:

151964

Hom.:

5412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.261

AC:

39748

AN:

152080

Hom.:

5422

Cov.:

AF XY:

0.265

AC XY:

19673

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.215

AC:

8904

AN:

41508

American (AMR)

AF:

0.356

AC:

5446

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

785

AN:

3472

East Asian (EAS)

AF:

0.113

AC:

585

AN:

5182

South Asian (SAS)

AF:

0.202

AC:

973

AN:

4822

European-Finnish (FIN)

AF:

0.358

AC:

3766

AN:

10518

Middle Eastern (MID)

AF:

0.229

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.273

AC:

18535

AN:

67980

Other (OTH)

AF:

0.252

AC:

533

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1533

3065

4598

6130

7663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.246

Hom.:

2460

Bravo

AF:

0.261

Asia WGS

AF:

0.175

AC:

611

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.2

(source)

DANN

Benign

0.49

PhyloP100

-1.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over