4-47653713-A-G

Variant names:

• chr4-47653713-A-G
• rs3805392
• NM_006587.4:c.1736-53T>C

Variant summary

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

The NM_006587.4(CORIN):​c.1736-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,446,900 control chromosomes in the GnomAD database, including 12,033 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 0.094 (1224 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10809 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 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.1736-53T>C		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.1424-53T>C		intron	N/A	NP_001265514.1
	CORIN	NM_001278586.2		c.1625-53T>C		intron	N/A	NP_001265515.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.1736-53T>C		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.1625-53T>C		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.1535-53T>C		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14337 AN: 152084 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.108 AC: 139348 AN: 1294698 Hom.: 10809 AF XY: 0.108 AC XY: 70151 AN XY: 651316

African (AFR) AF: 0.0247 AC: 742 AN: 30036

American (AMR) AF: 0.197 AC: 8534 AN: 43396

Ashkenazi Jewish (ASJ) AF: 0.0918 AC: 2282 AN: 24866

East Asian (EAS) AF: 0.472 AC: 18209 AN: 38562

South Asian (SAS) AF: 0.125 AC: 10167 AN: 81332

European-Finnish (FIN) AF: 0.114 AC: 6013 AN: 52896

Middle Eastern (MID) AF: 0.0915 AC: 489 AN: 5344

European-Non Finnish (NFE) AF: 0.0900 AC: 86730 AN: 963446

Other (OTH) AF: 0.113 AC: 6182 AN: 54820

GnomAD4 genome AF: 0.0942 AC: 14344 AN: 152202 Hom.: 1224 Cov.: 32 AF XY: 0.0971 AC XY: 7223 AN XY: 74416

African (AFR) AF: 0.0280 AC: 1162 AN: 41546

American (AMR) AF: 0.133 AC: 2035 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2427 AN: 5156

South Asian (SAS) AF: 0.138 AC: 666 AN: 4824

European-Finnish (FIN) AF: 0.117 AC: 1244 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0909 AC: 6183 AN: 68002

Other (OTH) AF: 0.103 AC: 218 AN: 2110

Alfa AF: 0.0849 Hom.: 84

Bravo AF: 0.0974

Asia WGS AF: 0.257 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-1.2
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: rs3805392; hg19: chr4-47655730; COSMIC: COSV56686467; COSMIC: COSV56686467;