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GeneBe

4-47603404-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_006587.4(CORIN):c.2805C>A(p.Gly935=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,613,732 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 32 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 32 hom. )

Consequence

CORIN
NM_006587.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.36
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-47603404-G-T is Benign according to our data. Variant chr4-47603404-G-T is described in ClinVar as [Benign]. Clinvar id is 785089.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.36 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1718/152194) while in subpopulation AFR AF= 0.0383 (1591/41516). AF 95% confidence interval is 0.0368. There are 32 homozygotes in gnomad4. There are 808 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1713 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CORINNM_006587.4 linkuse as main transcriptc.2805C>A p.Gly935= synonymous_variant 20/22 ENST00000273857.9
CORINNM_001278585.2 linkuse as main transcriptc.2493C>A p.Gly831= synonymous_variant 18/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CORINENST00000273857.9 linkuse as main transcriptc.2805C>A p.Gly935= synonymous_variant 20/221 NM_006587.4 P2Q9Y5Q5-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0113
AC:
1713
AN:
152076
Hom.:
31
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0383
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00282
Gnomad ASJ
AF:
0.0167
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000829
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00374
AC:
930
AN:
248368
Hom.:
15
AF XY:
0.00290
AC XY:
390
AN XY:
134352
show subpopulations
Gnomad AFR exome
AF:
0.0406
Gnomad AMR exome
AF:
0.00191
Gnomad ASJ exome
AF:
0.0167
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000153
Gnomad OTH exome
AF:
0.00295
GnomAD4 exome
AF:
0.00146
AC:
2140
AN:
1461538
Hom.:
32
Cov.:
32
AF XY:
0.00125
AC XY:
908
AN XY:
727066
show subpopulations
Gnomad4 AFR exome
AF:
0.0395
Gnomad4 AMR exome
AF:
0.00190
Gnomad4 ASJ exome
AF:
0.0157
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000791
Gnomad4 OTH exome
AF:
0.00361
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0113
AC:
1718
AN:
152194
Hom.:
32
Cov.:
32
AF XY:
0.0109
AC XY:
808
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0383
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.0167
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00690
Hom.:
6
Bravo
AF:
0.0124
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000415

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
7.2
Dann
Benign
0.68

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

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

Other links and lift over

dbSNP: rs73815721; hg19: chr4-47605421; API