rs11934749

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 16/21 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORIN	NM_006587.4	c.1574A>T	p.His525Leu	missense_variant	11/22	ENST00000273857.9
CORIN	NM_001278585.2	c.1262A>T	p.His421Leu	missense_variant	9/20
CORIN	NM_001278586.2	c.1463A>T	p.His488Leu	missense_variant	10/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORIN	ENST00000273857.9	c.1574A>T	p.His525Leu	missense_variant	11/22	1	NM_006587.4	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;.;T;.;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.10	T;T;T;T;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.42	T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.59	N;.;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.0	N;.;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.75	T;.;T;T;T;T
Sift4G	Uncertain	0.0050	D;D;D;D;D;T
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11934749; hg19: chr4-47667064;