Variant 1-85582843-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000451137.7(CCN1):c.947C>G(p.Ser316Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00682 in 1,614,154 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S316A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0046 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 42 hom. )

Consequence

CCN1
ENST00000451137.7 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.26

Variant links:

Genes affected

CCN1 (HGNC:2654): (cellular communication network factor 1) The secreted protein encoded by this gene is growth factor-inducible and promotes the adhesion of endothelial cells. The encoded protein interacts with several integrins and with heparan sulfate proteoglycan. This protein also plays a role in cell proliferation, differentiation, angiogenesis, apoptosis, and extracellular matrix formation. [provided by RefSeq, Sep 2011]

CCN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024793953).

BP6

Variant 1-85582843-C-G is Benign according to our data. Variant chr1-85582843-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 712918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 694 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCN1	NM_001554.5 linkuse as main transcript	c.947C>G	p.Ser316Cys	missense_variant	5/5	ENST00000451137.7	NP_001545.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCN1	ENST00000451137.7 linkuse as main transcript	c.947C>G	p.Ser316Cys	missense_variant	5/5	1	NM_001554.5	ENSP00000398736	P1

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

694

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00725

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00473

AC:

1189

AN:

251432

Hom.:

AF XY:

0.00500

AC XY:

680

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00312

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.00360

Gnomad NFE exome

AF:

0.00741

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00706

AC:

10317

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00695

AC XY:

5054

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00326

Gnomad4 FIN exome

AF:

0.00406

Gnomad4 NFE exome

AF:

0.00824

Gnomad4 OTH exome

AF:

0.00710

GnomAD4 genome

AF:

0.00456

AC:

694

AN:

152272

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00725

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00607

Hom.:

Bravo

AF:

0.00485

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00471

AC:

572

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00752

EpiControl

AF:

0.00830

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.015

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.4

REVEL

Benign

0.23

Sift

Benign

0.046

Sift4G

Benign

0.16

Polyphen

0.99

Vest4

0.47

MVP

0.34

MPC

0.83

ClinPred

0.017

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over