4-47624017-C-T

Variant names:

• chr4-47624017-C-T
• rs1344122
• NM_006587.4:c.2316-69G>A

Variant summary

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

The NM_006587.4(CORIN):​c.2316-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,296,434 control chromosomes in the GnomAD database, including 47,557 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 0.27 (5657 hom., cov: 32)
  • Exomes 𝑓: 0.27 (41900 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 8 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=-0.72).
• 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.2316-69G>A		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.2004-69G>A		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.2316-69G>A		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.2205-69G>A		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.2115-69G>A		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40906 AN: 151966 Hom.: 5648 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.265 AC: 303572 AN: 1144348 Hom.: 41900 AF XY: 0.262 AC XY: 153007 AN XY: 583950

African (AFR) AF: 0.234 AC: 6268 AN: 26822

American (AMR) AF: 0.417 AC: 17652 AN: 42322

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 5567 AN: 23900

East Asian (EAS) AF: 0.143 AC: 5433 AN: 38024

South Asian (SAS) AF: 0.209 AC: 16413 AN: 78504

European-Finnish (FIN) AF: 0.338 AC: 17407 AN: 51442

Middle Eastern (MID) AF: 0.220 AC: 1129 AN: 5138

European-Non Finnish (NFE) AF: 0.267 AC: 220859 AN: 828410

Other (OTH) AF: 0.258 AC: 12844 AN: 49786

GnomAD4 genome AF: 0.269 AC: 40934 AN: 152086 Hom.: 5657 Cov.: 32 AF XY: 0.272 AC XY: 20204 AN XY: 74350

African (AFR) AF: 0.244 AC: 10140 AN: 41510

American (AMR) AF: 0.352 AC: 5377 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3470

East Asian (EAS) AF: 0.112 AC: 579 AN: 5178

South Asian (SAS) AF: 0.201 AC: 968 AN: 4808

European-Finnish (FIN) AF: 0.358 AC: 3785 AN: 10570

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

European-Non Finnish (NFE) AF: 0.273 AC: 18534 AN: 67962

Other (OTH) AF: 0.257 AC: 542 AN: 2106

Alfa AF: 0.264 Hom.: 869

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
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		0.32
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: rs1344122; hg19: chr4-47626034; COSMIC: COSV56692236;