dbSNP rs55821538: CORIN:c.1958-4C>T (chr4-47643260-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006587.4(CORIN):c.1958-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,588,648 control chromosomes in the GnomAD database, including 509 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 18 hom., cov: 33)

Exomes 𝑓: 0.023 ( 491 hom. )

Consequence

CORIN
NM_006587.4 splice_region, intron

Scores

Splicing: ADA: 0.0004815

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

Variant links:

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 links:

LOC105374444 (HGNC:):

LOC105374444 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2253/152254) while in subpopulation NFE AF= 0.0251 (1708/68032). AF 95% confidence interval is 0.0241. There are 18 homozygotes in gnomad4. There are 1004 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2253 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORIN	NM_006587.4 link	c.1958-4C>T		splice_region_variant, intron_variant	Intron 14 of 21	ENST00000273857.9	NP_006578.2	Q9Y5Q5-1B4E2W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9 link	c.1958-4C>T		splice_region_variant, intron_variant	Intron 14 of 21	1	NM_006587.4	ENSP00000273857.4		Q9Y5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2254

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00401

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00839

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00727

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0251

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0169

AC:

3975

AN:

234796

Hom.:

AF XY:

0.0170

AC XY:

2157

AN XY:

126600

show subpopulations

Gnomad AFR exome

AF:

0.00331

Gnomad AMR exome

AF:

0.00697

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00995

Gnomad FIN exome

AF:

0.0182

Gnomad NFE exome

AF:

0.0263

Gnomad OTH exome

AF:

0.0179

GnomAD4 exome

AF:

0.0229

AC:

32836

AN:

1436394

Hom.:

491

Cov.:

AF XY:

0.0226

AC XY:

16045

AN XY:

711194

show subpopulations

Gnomad4 AFR exome

AF:

0.00326

Gnomad4 AMR exome

AF:

0.00684

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.0000765

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.0267

Gnomad4 OTH exome

AF:

0.0185

GnomAD4 genome

AF:

0.0148

AC:

2253

AN:

152254

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1004

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00399

Gnomad4 AMR

AF:

0.00838

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00707

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.0251

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00289

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00048

dbscSNV1_RF

Benign

0.032

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over