chr4-47645035-G-A

Variant names:

• chr4-47645035-G-A
• rs61759692
• NM_006587.4:c.1957+46C>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.1957+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,101,792 control chromosomes in the GnomAD database, including 488 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 0.022 (48 hom., cov: 32)
  • Exomes 𝑓: 0.027 (440 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 1 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=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0216 (3283/152246) while in subpopulation NFE AF = 0.033 (2241/68006). AF 95% confidence interval is 0.0318. There are 48 homozygotes in GnomAd4. There are 1549 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 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.1957+46C>T		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.1645+46C>T		intron	N/A	NP_001265514.1
	CORIN	NM_001278586.2		c.1846+46C>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.1957+46C>T		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.1846+46C>T		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.1756+46C>T		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3282 AN: 152126 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.00570

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0212 AC: 4768 AN: 225128 AF XY: 0.0216

Gnomad AFR exome AF: 0.00532

Gnomad AMR exome AF: 0.00596

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0370

Gnomad NFE exome AF: 0.0320

Gnomad OTH exome AF: 0.0195

GnomAD4 exome AF: 0.0272 AC: 25847 AN: 949546 Hom.: 440 Cov.: 12 AF XY: 0.0266 AC XY: 13053 AN XY: 490916

African (AFR) AF: 0.00492 AC: 112 AN: 22774

American (AMR) AF: 0.00668 AC: 246 AN: 36806

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 269 AN: 21556

East Asian (EAS) AF: 0.00 AC: 0 AN: 36828

South Asian (SAS) AF: 0.00576 AC: 403 AN: 69994

European-Finnish (FIN) AF: 0.0352 AC: 1839 AN: 52298

Middle Eastern (MID) AF: 0.00425 AC: 20 AN: 4706

European-Non Finnish (NFE) AF: 0.0331 AC: 21906 AN: 661438

Other (OTH) AF: 0.0244 AC: 1052 AN: 43146

GnomAD4 genome AF: 0.0216 AC: 3283 AN: 152246 Hom.: 48 Cov.: 32 AF XY: 0.0208 AC XY: 1549 AN XY: 74444

African (AFR) AF: 0.00568 AC: 236 AN: 41556

American (AMR) AF: 0.0122 AC: 186 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00727 AC: 35 AN: 4816

European-Finnish (FIN) AF: 0.0399 AC: 423 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0330 AC: 2241 AN: 68006

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.0216 Hom.: 21

Bravo AF: 0.0182

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.42
DANN	Benign	0.44
PhyloP100		0.040
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: rs61759692; hg19: chr4-47647052;