rs11934749

Variant names:

• chr4-47665047-T-A
• rs11934749
• NM_006587.4:c.1574A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-47665047-T-A
• chr4-47665047-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006587.4(CORIN):​c.1574A>T​(p.His525Leu) 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. H525Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CORIN NM_006587.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 38 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42066777).

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.1574A>T	p.His525Leu	missense	Exon 11 of 22	NP_006578.2
	CORIN	NM_001278585.2		c.1262A>T	p.His421Leu	missense	Exon 9 of 20	NP_001265514.1	A0A087X1D5
	CORIN	NM_001278586.2		c.1463A>T	p.His488Leu	missense	Exon 10 of 14	NP_001265515.1	J3KR83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.1574A>T	p.His525Leu	missense	Exon 11 of 22	ENSP00000273857.4	Q9Y5Q5-1
	CORIN	ENST00000961995.1		c.1574A>T	p.His525Leu	missense	Exon 11 of 23	ENSP00000632054.1
	CORIN	ENST00000961980.1		c.1556A>T	p.His519Leu	missense	Exon 11 of 22	ENSP00000632039.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 179374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.53
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.59	N
PhyloP100		1.7
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.21
Sift	Benign	0.75	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.017	B
Vest4		0.20
MutPred		0.81		Gain of glycosylation at T522 (P = 0.06)
MVP		0.81
MPC		0.069
ClinPred		0.34	T
GERP RS		4.3
Varity_R		0.10
gMVP		0.52
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11934749; hg19: chr4-47667064;