4-47623794-TAA-TA

Variant names:

• chr4-47623794-TA-T
• rs3215139
• NM_006587.4:c.2366-50delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006587.4(CORIN):​c.2366-50delT 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 1,611,906 control chromosomes in the GnomAD database, including 59,634 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (5647 hom., cov: 22)
  • Exomes 𝑓: 0.27 (53987 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 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.2366-50delT		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.2054-50delT		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.2366-50delT		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.2255-50delT		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.2165-50delT		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40885 AN: 151986 Hom.: 5638 Cov.: 22

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.275 AC: 69123 AN: 251118 AF XY: 0.268

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.0958

Gnomad FIN exome AF: 0.340

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.267 AC: 389533 AN: 1459802 Hom.: 53987 Cov.: 20 AF XY: 0.264 AC XY: 191770 AN XY: 726382

African (AFR) AF: 0.234 AC: 7818 AN: 33434

American (AMR) AF: 0.416 AC: 18619 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 6075 AN: 26118

East Asian (EAS) AF: 0.141 AC: 5606 AN: 39686

South Asian (SAS) AF: 0.208 AC: 17958 AN: 86220

European-Finnish (FIN) AF: 0.338 AC: 18032 AN: 53400

Middle Eastern (MID) AF: 0.226 AC: 1302 AN: 5760

European-Non Finnish (NFE) AF: 0.269 AC: 298588 AN: 1110158

Other (OTH) AF: 0.258 AC: 15535 AN: 60310

GnomAD4 genome AF: 0.269 AC: 40913 AN: 152104 Hom.: 5647 Cov.: 22 AF XY: 0.272 AC XY: 20192 AN XY: 74360

African (AFR) AF: 0.244 AC: 10121 AN: 41522

American (AMR) AF: 0.352 AC: 5378 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3468

East Asian (EAS) AF: 0.112 AC: 580 AN: 5176

South Asian (SAS) AF: 0.202 AC: 973 AN: 4822

European-Finnish (FIN) AF: 0.357 AC: 3769 AN: 10562

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18536 AN: 67952

Other (OTH) AF: 0.259 AC: 547 AN: 2112

Alfa AF: 0.268 Hom.: 970

Bravo AF: 0.269

Asia WGS AF: 0.175 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3215139; hg19: chr4-47625811; COSMIC: COSV56693567;