4-47595743-A-T

Position:

• chr4-47595743-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006587.4(CORIN):​c.3107T>A​(p.Ile1036Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CORIN NM_006587.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORIN	NM_006587.4	c.3107T>A	p.Ile1036Asn	missense_variant	22/22	ENST00000273857.9	NP_006578.2
CORIN	NM_001278585.2	c.2795T>A	p.Ile932Asn	missense_variant	20/20		NP_001265514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.3107T>A	p.Ile1036Asn	missense_variant	22/22	1	NM_006587.4	ENSP00000273857.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.3107T>A (p.I1036N) alteration is located in exon 22 (coding exon 22) of the CORIN gene. This alteration results from a T to A substitution at nucleotide position 3107, causing the isoleucine (I) at amino acid position 1036 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	T;.;.;T;.
Eigen	Benign	0.088
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Uncertain	0.072	D
MutationAssessor	Benign	0.21	N;.;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.97	N;.;N;N;N
REVEL	Uncertain	0.54
Sift	Benign	0.068	T;.;T;T;T
Sift4G	Uncertain	0.014	D;D;D;D;D
Polyphen		0.99	D;.;.;.;.
Vest4		0.59
MutPred		0.48		Gain of disorder (P = 0.0085);.;.;.;.;
MVP		0.95
MPC		0.34
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.30
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-47597760;