rs4694863

chr4-47633569-A-Cchr4-47633569-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006587.4(CORIN):c.2199-7048T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,080 control chromosomes in the GnomAD database, including 5,422 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 0.26 (5422 hom., cov: 33)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORIN	NM_006587.4	c.2199-7048T>G		intron_variant		ENST00000273857.9
LOC105374444	XR_007058109.1	n.384+2004A>C		intron_variant, non_coding_transcript_variant
CORIN	NM_001278585.2	c.1887-7048T>G		intron_variant
LOC105374444	XR_925284.3	n.591+2004A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORIN	ENST00000273857.9	c.2199-7048T>G		intron_variant		1	NM_006587.4	P2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39717 AN: 151964 Hom.: 5412 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.261 AC: 39748 AN: 152080 Hom.: 5422 Cov.: 33 AF XY: 0.265 AC XY: 19673 AN XY: 74328

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.252

Alfa AF: 0.243 Hom.: 2167

Bravo AF: 0.261

Asia WGS AF: 0.175 AC: 611 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.2
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs4694863; hg19: chr4-47635586;