Genetic Variant NM_006587.4:c.409+69C>T (chr4-47786656-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006587.4(CORIN):c.409+69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00069 in 1,214,422 control chromosomes in the GnomAD database, including 2 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 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

CORIN
NM_006587.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS2

High Homozygotes in GnomAd4 at 2 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4 link	c.409+69C>T	intron_variant	Intron 3 of 21	ENST00000273857.9	NP_006578.2	Q9Y5Q5-1B4E2W9
CORIN	NM_001278585.2 link	c.208+20247C>T	intron_variant	Intron 2 of 19		NP_001265514.1	Q9Y5Q5A0A087X1D5B4E1Y7B4E2W9
CORIN	NM_001278586.2 link	c.409+69C>T	intron_variant	Intron 3 of 13		NP_001265515.1	J3KR83B4E2W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9 link	c.409+69C>T		intron_variant	Intron 3 of 21	1	NM_006587.4	ENSP00000273857.4		Q9Y5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.00326

AC:

496

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.000321

AC:

341

AN:

1062144

Hom.:

AF XY:

0.000290

AC XY:

157

AN XY:

541406

show subpopulations

African (AFR)

AF:

0.0120

AC:

296

AN:

24734

American (AMR)

AF:

0.000305

AC:

AN:

36042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21272

East Asian (EAS)

AF:

0.00

AC:

AN:

37620

South Asian (SAS)

AF:

0.00

AC:

AN:

71036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51788

Middle Eastern (MID)

AF:

0.000621

AC:

AN:

4830

European-Non Finnish (NFE)

AF:

0.00000130

AC:

AN:

767864

Other (OTH)

AF:

0.000639

AC:

AN:

46958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00326

AC:

497

AN:

152278

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

215

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0116

AC:

483

AN:

41564

American (AMR)

AF:

0.000589

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00184

Hom.:

Bravo

AF:

0.00385

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.14

(source)

DANN

Benign

0.66

PhyloP100

-1.3

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