chr4-47623794-TA-T

Position:

• chr4-47623794-TA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000273857.9(CORIN):​c.2366-50del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,611,906 control chromosomes in the GnomAD database, including 59,634 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (5647 hom., cov: 22)
  • Exomes 𝑓: 0.27 (53987 hom.)
• Consequence: CORIN ENST00000273857.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610

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]

LOC105374444 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORIN	NM_006587.4	c.2366-50del		intron_variant		ENST00000273857.9	NP_006578.2
LOC105374444	XR_007058109.1	n.87+26del		intron_variant, non_coding_transcript_variant
CORIN	NM_001278585.2	c.2054-50del		intron_variant			NP_001265514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.2366-50del		intron_variant		1	NM_006587.4	ENSP00000273857	P2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40885 AN: 151986 Hom.: 5638 Cov.: 22

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.262

GnomAD3 exomes AF: 0.275 AC: 69123 AN: 251118 Hom.: 10445 AF XY: 0.268 AC XY: 36366 AN XY: 135720

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.0958

Gnomad SAS exome AF: 0.207

Gnomad FIN exome AF: 0.340

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.267 AC: 389533 AN: 1459802 Hom.: 53987 Cov.: 20 AF XY: 0.264 AC XY: 191770 AN XY: 726382

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.269 AC: 40913 AN: 152104 Hom.: 5647 Cov.: 22 AF XY: 0.272 AC XY: 20192 AN XY: 74360

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.259

Alfa AF: 0.268 Hom.: 970

Bravo AF: 0.269

Asia WGS AF: 0.175 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3215139; hg19: chr4-47625811;