chr4-47641846-T-C

Variant names:

• chr4-47641846-T-C
• rs17462783
• NM_006587.4:c.2198+74A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006587.4(CORIN):​c.2198+74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 1,551,960 control chromosomes in the GnomAD database, including 5,790 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.088 (672 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5118 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	NM_006587.4	MANE Select	c.2198+74A>G		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.1886+74A>G		intron	N/A	NP_001265514.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.2198+74A>G		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.2087+74A>G		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.1997+74A>G		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13445 AN: 152122 Hom.: 669 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.0740

GnomAD4 exome AF: 0.0817 AC: 114313 AN: 1399720 Hom.: 5118 AF XY: 0.0806 AC XY: 55917 AN XY: 693448

African (AFR) AF: 0.136 AC: 4368 AN: 32184

American (AMR) AF: 0.0375 AC: 1596 AN: 42578

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 1416 AN: 23958

East Asian (EAS) AF: 0.00223 AC: 85 AN: 38072

South Asian (SAS) AF: 0.0362 AC: 2920 AN: 80708

European-Finnish (FIN) AF: 0.0601 AC: 2925 AN: 48662

Middle Eastern (MID) AF: 0.0719 AC: 397 AN: 5520

European-Non Finnish (NFE) AF: 0.0900 AC: 96340 AN: 1070494

Other (OTH) AF: 0.0741 AC: 4266 AN: 57544

GnomAD4 genome AF: 0.0884 AC: 13459 AN: 152240 Hom.: 672 Cov.: 33 AF XY: 0.0847 AC XY: 6307 AN XY: 74442

African (AFR) AF: 0.135 AC: 5625 AN: 41526

American (AMR) AF: 0.0502 AC: 768 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3470

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5188

South Asian (SAS) AF: 0.0298 AC: 144 AN: 4828

European-Finnish (FIN) AF: 0.0593 AC: 629 AN: 10612

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0865 AC: 5882 AN: 68004

Other (OTH) AF: 0.0766 AC: 162 AN: 2116

Alfa AF: 0.0904 Hom.: 98

Bravo AF: 0.0893

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.0
DANN	Benign	0.65
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs17462783; hg19: chr4-47643863; COSMIC: COSV56697798; COSMIC: COSV56697798;