rs61760501

Variant names:

• chr4-47677999-C-T
• rs61760501
• NM_006587.4:c.1188G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006587.4(CORIN):​c.1188G>A​(p.Thr396Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,614,052 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (11 hom.)
• Consequence: CORIN NM_006587.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.83
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-47677999-C-T is Benign according to our data. Variant chr4-47677999-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 778859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.83 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 11 Unknown gene

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.1188G>A	p.Thr396Thr	synonymous	Exon 9 of 22	NP_006578.2
	CORIN	NM_001278585.2		c.876G>A	p.Thr292Thr	synonymous	Exon 7 of 20	NP_001265514.1	A0A087X1D5
	CORIN	NM_001278586.2		c.1077G>A	p.Thr359Thr	synonymous	Exon 8 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.1188G>A	p.Thr396Thr	synonymous	Exon 9 of 22	ENSP00000273857.4	Q9Y5Q5-1
	CORIN	ENST00000961995.1		c.1188G>A	p.Thr396Thr	synonymous	Exon 9 of 23	ENSP00000632054.1
	CORIN	ENST00000961980.1		c.1170G>A	p.Thr390Thr	synonymous	Exon 9 of 22	ENSP00000632039.1

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 310 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00334

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00222 AC: 558 AN: 250888 AF XY: 0.00233

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.000872

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00312

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00317 AC: 4639 AN: 1461752 Hom.: 11 Cov.: 31 AF XY: 0.00318 AC XY: 2315 AN XY: 727190

African (AFR) AF: 0.000358 AC: 12 AN: 33478

American (AMR) AF: 0.00264 AC: 118 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 53 AN: 26134

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39676

South Asian (SAS) AF: 0.00198 AC: 171 AN: 86254

European-Finnish (FIN) AF: 0.000580 AC: 31 AN: 53420

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00367 AC: 4085 AN: 1111912

Other (OTH) AF: 0.00243 AC: 147 AN: 60388

GnomAD4 genome AF: 0.00204 AC: 310 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.00167 AC XY: 124 AN XY: 74472

African (AFR) AF: 0.000794 AC: 33 AN: 41572

American (AMR) AF: 0.00176 AC: 27 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4810

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00334 AC: 227 AN: 68016

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00293 Hom.: 0

Bravo AF: 0.00207

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00360

EpiControl AF: 0.00356

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.56
PhyloP100		-1.8
Mutation Taster		=100/0	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: rs61760501; hg19: chr4-47680016;