chr4-47643167-T-C

Variant names:

• chr4-47643167-T-C
• rs144722161
• NM_006587.4:c.2047A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006587.4(CORIN):​c.2047A>G​(p.Ser683Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S683C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CORIN NM_006587.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 4 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)

LOC105374444 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14467722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4	c.2047A>G	p.Ser683Gly	missense_variant	Exon 15 of 22	ENST00000273857.9	NP_006578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.2047A>G	p.Ser683Gly	missense_variant	Exon 15 of 22	1	NM_006587.4	ENSP00000273857.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00000872 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.49
DEOGEN2	Benign	0.21	T;.;.;T;.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.67
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.66	T;T;T;T;T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	-1.4	N;.;.;.;.;.
PhyloP100		2.9
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.21	N;.;N;N;N;N
REVEL	Benign	0.29
Sift	Benign	1.0	T;.;T;T;T;T
Sift4G	Benign	0.46	T;T;T;T;T;T
Polyphen		0.015	B;.;.;.;.;.
Vest4		0.27
MutPred		0.50		Gain of glycosylation at S683 (P = 0.0426);.;.;.;.;.;
MVP		0.91
MPC		0.055
ClinPred		0.054	T
GERP RS		2.6
Varity_R		0.037
gMVP		0.62
Mutation Taster		=82/18	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: rs144722161; hg19: chr4-47645184;