4-47596281-T-C

Variant names:

• chr4-47596281-T-C
• rs17462424
• NM_006587.4:c.2947-378A>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.2947-378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,900 control chromosomes in the GnomAD database, including 9,961 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 0.36 (9961 hom., cov: 31)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4	c.2947-378A>G		intron_variant	Intron 21 of 21	ENST00000273857.9	NP_006578.2
CORIN	NM_001278585.2	c.2635-378A>G		intron_variant	Intron 19 of 19		NP_001265514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.2947-378A>G		intron_variant	Intron 21 of 21	1	NM_006587.4	ENSP00000273857.4

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54228 AN: 151780 Hom.: 9947 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.357 AC: 54277 AN: 151900 Hom.: 9961 Cov.: 31 AF XY: 0.356 AC XY: 26458 AN XY: 74232

African (AFR) AF: 0.381 AC: 15776 AN: 41412

American (AMR) AF: 0.400 AC: 6098 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3466

East Asian (EAS) AF: 0.120 AC: 622 AN: 5168

South Asian (SAS) AF: 0.247 AC: 1188 AN: 4812

European-Finnish (FIN) AF: 0.415 AC: 4383 AN: 10556

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24340 AN: 67942

Other (OTH) AF: 0.335 AC: 705 AN: 2106

Alfa AF: 0.350 Hom.: 4809

Bravo AF: 0.357

Asia WGS AF: 0.223 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.74
PhyloP100		0.63
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: rs17462424; hg19: chr4-47598298;