rs17601068

Positions:

• chr4-47617786-G-A
• chr4-47617786-G-C

Variant summary

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

The NM_006587.4(CORIN):​c.2540+5785C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,170 control chromosomes in the GnomAD database, including 1,350 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 0.11 (1350 hom., cov: 32)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORIN	NM_006587.4	c.2540+5785C>T		intron_variant		ENST00000273857.9	NP_006578.2
CORIN	NM_001278585.2	c.2228+5785C>T		intron_variant			NP_001265514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.2540+5785C>T		intron_variant		1	NM_006587.4	ENSP00000273857	P2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16735 AN: 152052 Hom.: 1353 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0964

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.110 AC: 16742 AN: 152170 Hom.: 1350 Cov.: 32 AF XY: 0.112 AC XY: 8368 AN XY: 74386

Gnomad4 AFR AF: 0.0806

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0964

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0910

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0938 Hom.: 312

Bravo AF: 0.117

Asia WGS AF: 0.258 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.69

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: rs17601068; hg19: chr4-47619803;