rs61760500

Variant names:

• chr4-47677925-G-A
• rs61760500
• NM_006587.4:c.1249+13C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-47677925-G-A
• chr4-47677925-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006587.4(CORIN):​c.1249+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,570,902 control chromosomes in the GnomAD database, including 105 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 0.0053 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (97 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• 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).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00532 (810/152228) while in subpopulation SAS AF = 0.0241 (116/4816). AF 95% confidence interval is 0.0205. There are 8 homozygotes in GnomAd4. There are 393 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 Unknown gene

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.1249+13C>T		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.937+13C>T		intron	N/A	NP_001265514.1
	CORIN	NM_001278586.2		c.1138+13C>T		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.1249+13C>T		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.1138+13C>T		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.1048+13C>T		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.00533 AC: 811 AN: 152110 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00547

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00641

Gnomad OTH AF: 0.00862

GnomAD2 exomes AF: 0.00888 AC: 2223 AN: 250422 AF XY: 0.0102

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00588

Gnomad NFE exome AF: 0.00667

Gnomad OTH exome AF: 0.00933

GnomAD4 exome AF: 0.00711 AC: 10088 AN: 1418674 Hom.: 97 Cov.: 26 AF XY: 0.00776 AC XY: 5496 AN XY: 708498

African (AFR) AF: 0.000980 AC: 32 AN: 32666

American (AMR) AF: 0.00351 AC: 157 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0146 AC: 377 AN: 25846

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39470

South Asian (SAS) AF: 0.0300 AC: 2562 AN: 85306

European-Finnish (FIN) AF: 0.00560 AC: 299 AN: 53394

Middle Eastern (MID) AF: 0.0174 AC: 99 AN: 5682

European-Non Finnish (NFE) AF: 0.00567 AC: 6079 AN: 1072690

Other (OTH) AF: 0.00809 AC: 477 AN: 58954

GnomAD4 genome AF: 0.00532 AC: 810 AN: 152228 Hom.: 8 Cov.: 32 AF XY: 0.00528 AC XY: 393 AN XY: 74432

African (AFR) AF: 0.00111 AC: 46 AN: 41540

American (AMR) AF: 0.00386 AC: 59 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0241 AC: 116 AN: 4816

European-Finnish (FIN) AF: 0.00547 AC: 58 AN: 10594

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00641 AC: 436 AN: 68008

Other (OTH) AF: 0.00853 AC: 18 AN: 2110

Alfa AF: 0.00743 Hom.: 0

Bravo AF: 0.00434

Asia WGS AF: 0.0110 AC: 38 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	0.10
DANN	Benign	0.54
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism

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: rs61760500; hg19: chr4-47679942; COSMIC: COSV56688488; COSMIC: COSV56688488;