Genetic Variant CCN1:c.-107C>A (chr1-85580878-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001554.5(CCN1):c.-107C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,091,380 control chromosomes in the GnomAD database, including 150,051 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 21972 hom., cov: 32)

Exomes 𝑓: 0.52 ( 128079 hom. )

Consequence

CCN1
NM_001554.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.01

Publications

11 publications found

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:

ENSG00000272691 (HGNC:):

ENSG00000272691 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCN1	NM_001554.5 link	c.-107C>A		5_prime_UTR_variant	Exon 1 of 5	ENST00000451137.7	NP_001545.2	O00622Q6FI18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCN1	ENST00000451137.7 link	c.-107C>A		5_prime_UTR_variant	Exon 1 of 5	1	NM_001554.5	ENSP00000398736.2		O00622

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

81100

AN:

151796

Hom.:

21948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.521

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.534

GnomAD4 exome

AF:

0.518

AC:

487052

AN:

939474

Hom.:

128079

Cov.:

AF XY:

0.522

AC XY:

239144

AN XY:

458412

show subpopulations

African (AFR)

AF:

0.606

AC:

11451

AN:

18890

American (AMR)

AF:

0.515

AC:

4685

AN:

9100

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

7542

AN:

14210

East Asian (EAS)

AF:

0.579

AC:

14948

AN:

25818

South Asian (SAS)

AF:

0.688

AC:

23642

AN:

34358

European-Finnish (FIN)

AF:

0.414

AC:

12028

AN:

29088

Middle Eastern (MID)

AF:

0.565

AC:

2271

AN:

4018

European-Non Finnish (NFE)

AF:

0.509

AC:

388960

AN:

764104

Other (OTH)

AF:

0.540

AC:

21525

AN:

39888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

11104

22208

33311

44415

55519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.534

AC:

81176

AN:

151906

Hom.:

21972

Cov.:

AF XY:

0.531

AC XY:

39416

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.600

AC:

24876

AN:

41452

American (AMR)

AF:

0.504

AC:

7707

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

1862

AN:

3468

East Asian (EAS)

AF:

0.599

AC:

3060

AN:

5108

South Asian (SAS)

AF:

0.681

AC:

3276

AN:

4814

European-Finnish (FIN)

AF:

0.398

AC:

4204

AN:

10554

Middle Eastern (MID)

AF:

0.620

AC:

181

AN:

292

European-Non Finnish (NFE)

AF:

0.507

AC:

34410

AN:

67904

Other (OTH)

AF:

0.534

AC:

1128

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1935

3870

5804

7739

9674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.520

Hom.:

2555

Bravo

AF:

0.540

Asia WGS

AF:

0.633

AC:

2199

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.0

(source)

DANN

Benign

0.79

PhyloP100

1.0

PromoterAI

-0.14

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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1-85580878-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over