chr4-47643044-G-A

Variant names:

• chr4-47643044-G-A
• rs55932196
• NM_006587.4:c.2068+102C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006587.4(CORIN):​c.2068+102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00981 in 1,578,336 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0099 (96 hom.)
• Consequence: CORIN NM_006587.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.70
• Publications: 1 publications found

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)

LOC105374444 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004630983).
• BP6: Variant 4-47643044-G-A is Benign according to our data. Variant chr4-47643044-G-A is described in ClinVar as Benign. ClinVar VariationId is 1695093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 Unknown gene

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	NM_006587.4	MANE Select	c.2068+102C>T		intron	N/A	NP_006578.2
	CORIN	NM_001278586.2		c.2059C>T	p.His687Tyr	missense	Exon 14 of 14	NP_001265515.1
	CORIN	NM_001278585.2		c.1756+102C>T		intron	N/A	NP_001265514.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORIN	ENST00000273857.9	TSL:1 MANE Select	c.2068+102C>T		intron	N/A	ENSP00000273857.4
	CORIN	ENST00000504584.1	TSL:2	c.2059C>T	p.His687Tyr	missense	Exon 14 of 14	ENSP00000423216.1
	CORIN	ENST00000505754.1	TSL:3	n.477C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00894 AC: 1361 AN: 152178 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00926 AC: 1823 AN: 196824 AF XY: 0.00907

Gnomad AFR exome AF: 0.00146

Gnomad AMR exome AF: 0.00513

Gnomad ASJ exome AF: 0.00917

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0220

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.00990 AC: 14119 AN: 1426040 Hom.: 96 Cov.: 32 AF XY: 0.00966 AC XY: 6824 AN XY: 706692

African (AFR) AF: 0.00123 AC: 40 AN: 32548

American (AMR) AF: 0.00512 AC: 202 AN: 39464

Ashkenazi Jewish (ASJ) AF: 0.00829 AC: 212 AN: 25560

East Asian (EAS) AF: 0.00 AC: 0 AN: 37916

South Asian (SAS) AF: 0.00272 AC: 225 AN: 82730

European-Finnish (FIN) AF: 0.0224 AC: 1034 AN: 46108

Middle Eastern (MID) AF: 0.00506 AC: 29 AN: 5734

European-Non Finnish (NFE) AF: 0.0109 AC: 11913 AN: 1096712

Other (OTH) AF: 0.00783 AC: 464 AN: 59268

GnomAD4 genome AF: 0.00892 AC: 1359 AN: 152296 Hom.: 9 Cov.: 33 AF XY: 0.00926 AC XY: 690 AN XY: 74474

African (AFR) AF: 0.00229 AC: 95 AN: 41562

American (AMR) AF: 0.00660 AC: 101 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0128 AC: 869 AN: 68020

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.00740 Hom.: 0

Bravo AF: 0.00754

TwinsUK AF: 0.00917 AC: 34

ALSPAC AF: 0.00882 AC: 34

ExAC AF: 0.00944 AC: 1137

Asia WGS AF: 0.000578 AC: 2 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CORIN-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.47
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.75	T
PhyloP100		1.7
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Vest4		0.097
MVP		0.63
ClinPred		0.078	T
GERP RS		2.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs55932196; hg19: chr4-47645061;