rs74701656

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -8 classification points (ACMG Germline Pathogenicity v2019). BS2BP4_Strong

The NM_006587.4(CORIN):c.409+69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00069 (AC=838) in the gnomAD database across 1,214,422 control chromosomes, including 2 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.0108. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

CORIN
NM_006587.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

preeclampsia/eclampsia 5
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CORIN links:

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new If you want to explore the variant's impact on the transcript NM_006587.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -8 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BS2Observed in healthy adult		≥2 homozygotes in gnomAD — observed in healthy adults (BS2); GnomAD homozygous count = 2.; Very high cumulative gnomAD AC = 838 (any gene).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_006587.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CORIN	NM_006587.4	MANE Select	c.409+69C>T	intron	N/A	NP_006578.2
CORIN	NM_001278585.2		c.208+20247C>T	intron	N/A	NP_001265514.1	A0A087X1D5
CORIN	NM_001278586.2		c.409+69C>T	intron	N/A	NP_001265515.1	J3KR83

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CORIN	ENST00000273857.9	TSL:1 MANE Select	c.409+69C>T	intron	N/A	ENSP00000273857.4	Q9Y5Q5-1
CORIN	ENST00000961995.1		c.409+69C>T	intron	N/A	ENSP00000632054.1	A0ACI8V9Q0
CORIN	ENST00000961980.1		c.409+69C>T	intron	N/A	ENSP00000632039.1	A0ACI8V9Y7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00326	AC:496	Hom:2	AN:152160	Cov:32
GnomAD4 exome	AF: 0.000321	AC:341	Hom:0	AN:1062144	Cov:
GnomAD4 genome	AF: 0.00326	AC:497	Hom:2	AN:152278	Cov:32
TOPMed (Bravo)	AF: 0.00385	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00240	AC:156	Hom:1	AN:64982	Cov:
Local & regional cohorts 2 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.00214	AC:5	Hom:0	AN:2342	Cov:
GenomeAsia100K	AF: 0.000289	AC:1	Hom:	AN:3478	Cov:

Showing 7 sources

Case/control cohorts

Cohort	Cases			Controls
Cohort	AF	AC	AN	AF	AC	AN
SCHEMA (Schizophrenia)	0.0000453	3	66216	0.0000396	5	126306

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Benign	0.37
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.66
GPN-Star LLR	N/A	0.49
GPN-Star score	N/A	-0.49
PhyloP100	Benign	-1.3

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Case/control cohorts

ClinVar

Computational Scores

Splicing Scores

Publications

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