rs17601068

Variant names:

• chr4-47617786-G-A
• rs17601068
• NM_006587.4:c.2540+5785C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-47617786-G-A
• chr4-47617786-G-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.2540+5785C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,170 control chromosomes in the GnomAD database, including 1,350 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 0.11 (1350 hom., cov: 32)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 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.2540+5785C>T		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.2228+5785C>T		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.2540+5785C>T		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.2429+5785C>T		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.2339+5785C>T		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16735 AN: 152052 Hom.: 1353 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0964

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.110 AC: 16742 AN: 152170 Hom.: 1350 Cov.: 32 AF XY: 0.112 AC XY: 8368 AN XY: 74386

African (AFR) AF: 0.0806 AC: 3347 AN: 41528

American (AMR) AF: 0.148 AC: 2261 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0964 AC: 334 AN: 3466

East Asian (EAS) AF: 0.467 AC: 2409 AN: 5156

South Asian (SAS) AF: 0.132 AC: 635 AN: 4816

European-Finnish (FIN) AF: 0.117 AC: 1243 AN: 10582

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0910 AC: 6192 AN: 68020

Other (OTH) AF: 0.113 AC: 238 AN: 2108

Alfa AF: 0.0938 Hom.: 351

Bravo AF: 0.117

Asia WGS AF: 0.258 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.69
PhyloP100		0.55
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: rs17601068; hg19: chr4-47619803;