rs55821538

Positions:

• chr4-47643260-G-A
• chr4-47643260-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006587.4(CORIN):​c.1958-4C>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0004815
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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=-0.51).
• 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/exons	MANE	Protein	UniProt
CORIN	NM_006587.4	c.1958-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000273857.9	NP_006578.2
LOC105374444	XR_007058109.1	n.2936-726G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORIN	ENST00000273857.9	c.1958-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006587.4	ENSP00000273857	P2

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2254 AN: 152136 Hom.: 18 Cov.: 33

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.: 53 AF XY: 0.0170 AC XY: 2157 AN XY: 126600

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.: 31 AF XY: 0.0226 AC XY: 16045 AN XY: 711194

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.: 18 Cov.: 33 AF XY: 0.0135 AC XY: 1004 AN XY: 74428

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.: 10

Bravo AF: 0.0137

Asia WGS AF: 0.00289 AC: 10 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	11
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

Other links and lift over

dbSNP: rs55821538; hg19: chr4-47645277;