chr4-47595732-G-C

Variant names:

• chr4-47595732-G-C
• rs76700540
• NM_006587.4:c.3118C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006587.4(CORIN):​c.3118C>G​(p.Leu1040Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000987 in 1,601,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (0 hom.)
• Consequence: CORIN NM_006587.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47
• Publications: 3 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19231516).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	NM_006587.4	MANE Select	c.3118C>G	p.Leu1040Val	missense	Exon 22 of 22	NP_006578.2
	CORIN	NM_001278585.2		c.2806C>G	p.Leu936Val	missense	Exon 20 of 20	NP_001265514.1	A0A087X1D5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.3118C>G	p.Leu1040Val	missense	Exon 22 of 22	ENSP00000273857.4	Q9Y5Q5-1
	CORIN	ENST00000961995.1		c.3193C>G	p.Leu1065Val	missense	Exon 23 of 23	ENSP00000632054.1
	CORIN	ENST00000961980.1		c.3100C>G	p.Leu1034Val	missense	Exon 22 of 22	ENSP00000632039.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000628 AC: 15 AN: 238902 AF XY: 0.0000697

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000128

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000100

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000987 AC: 143 AN: 1449324 Hom.: 0 Cov.: 30 AF XY: 0.000107 AC XY: 77 AN XY: 720854

African (AFR) AF: 0.00 AC: 0 AN: 32486

American (AMR) AF: 0.000122 AC: 5 AN: 41118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25362

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 83812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.000116 AC: 129 AN: 1108354

Other (OTH) AF: 0.000151 AC: 9 AN: 59758

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74446

African (AFR) AF: 0.0000241 AC: 1 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000118 Hom.: 0

Bravo AF: 0.0000831

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000219

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.017
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	0.093	D
MutationAssessor	Benign	0.34	N
PhyloP100		3.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.26
MVP		0.94
MPC		0.14
ClinPred		0.27	T
GERP RS		2.8
Varity_R		0.11
gMVP		0.66
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs76700540; hg19: chr4-47597749;