rs6447571

Variant names:

• chr4-47631100-T-C
• rs6447571
• NM_006587.4:c.2199-4579A>G

Variant summary

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

The NM_006587.4(CORIN):​c.2199-4579A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,164 control chromosomes in the GnomAD database, including 1,959 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 0.14 (1959 hom., cov: 32)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• 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)

LOC105374444 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 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.2199-4579A>G		intron	N/A	NP_006578.2
	CORIN	NM_001278585.2		c.1887-4579A>G		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.2199-4579A>G		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000505909.5	TSL:5	c.2088-4579A>G		intron	N/A	ENSP00000425401.1
	CORIN	ENST00000502252.5	TSL:2	c.1998-4579A>G		intron	N/A	ENSP00000424212.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21031 AN: 152046 Hom.: 1961 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0962

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.138 AC: 21041 AN: 152164 Hom.: 1959 Cov.: 32 AF XY: 0.140 AC XY: 10392 AN XY: 74378

African (AFR) AF: 0.180 AC: 7488 AN: 41510

American (AMR) AF: 0.151 AC: 2315 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 334 AN: 3472

East Asian (EAS) AF: 0.470 AC: 2423 AN: 5156

South Asian (SAS) AF: 0.133 AC: 639 AN: 4814

European-Finnish (FIN) AF: 0.118 AC: 1248 AN: 10606

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0915 AC: 6223 AN: 67998

Other (OTH) AF: 0.136 AC: 286 AN: 2106

Alfa AF: 0.104 Hom.: 614

Bravo AF: 0.148

Asia WGS AF: 0.259 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		-0.017
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: rs6447571; hg19: chr4-47633117;