4-47677911-T-C

Variant names:

• chr4-47677911-T-C
• rs2271036
• NM_006587.4:c.1249+27A>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.1249+27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,466,778 control chromosomes in the GnomAD database, including 57,637 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 0.31 (8627 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49010 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	NM_006587.4	MANE Select	c.1249+27A>G		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.937+27A>G		intron	N/A	NP_001265514.1
	CORIN	NM_001278586.2		c.1138+27A>G		intron	N/A	NP_001265515.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.1249+27A>G		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000961995.1		c.1249+27A>G		intron	N/A	ENSP00000632054.1
	CORIN	ENST00000961980.1		c.1231+27A>G		intron	N/A	ENSP00000632039.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47764 AN: 151896 Hom.: 8607 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.295

GnomAD2 exomes AF: 0.289 AC: 71890 AN: 248926 AF XY: 0.277

Gnomad AFR exome AF: 0.466

Gnomad AMR exome AF: 0.299

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.629

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.261 AC: 343505 AN: 1314764 Hom.: 49010 Cov.: 19 AF XY: 0.258 AC XY: 170604 AN XY: 662022

African (AFR) AF: 0.473 AC: 14504 AN: 30688

American (AMR) AF: 0.297 AC: 13171 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4203 AN: 25236

East Asian (EAS) AF: 0.618 AC: 24077 AN: 38952

South Asian (SAS) AF: 0.208 AC: 17321 AN: 83148

European-Finnish (FIN) AF: 0.269 AC: 14333 AN: 53272

Middle Eastern (MID) AF: 0.197 AC: 1087 AN: 5512

European-Non Finnish (NFE) AF: 0.245 AC: 239722 AN: 977908

Other (OTH) AF: 0.271 AC: 15087 AN: 55636

GnomAD4 genome AF: 0.315 AC: 47820 AN: 152014 Hom.: 8627 Cov.: 32 AF XY: 0.312 AC XY: 23172 AN XY: 74294

African (AFR) AF: 0.460 AC: 19052 AN: 41438

American (AMR) AF: 0.260 AC: 3969 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3468

East Asian (EAS) AF: 0.621 AC: 3206 AN: 5162

South Asian (SAS) AF: 0.206 AC: 991 AN: 4814

European-Finnish (FIN) AF: 0.270 AC: 2855 AN: 10560

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16407 AN: 67974

Other (OTH) AF: 0.300 AC: 631 AN: 2106

Alfa AF: 0.267 Hom.: 2123

Bravo AF: 0.325

Asia WGS AF: 0.422 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.24
PhyloP100		-3.0
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: rs2271036; hg19: chr4-47679928;