Genetic Variant CCN1:c.277+50G>C (chr1-85581628-G-C) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001554.5(CCN1):c.277+50G>C variant causes a intron change. The variant allele was found at a frequency of 0.193 in 1,573,466 control chromosomes in the GnomAD database, including 30,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2266 hom., cov: 33)

Exomes 𝑓: 0.20 ( 28441 hom. )

Consequence

CCN1
NM_001554.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.08

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 1-85581628-G-C is Benign according to our data. Variant chr1-85581628-G-C is described in ClinVar as Benign. ClinVar VariationId is 1178850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001554.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCN1	NM_001554.5	MANE Select	c.277+50G>C		intron	N/A	NP_001545.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCN1	ENST00000451137.7	TSL:1 MANE Select	c.277+50G>C	intron	N/A	ENSP00000398736.2	O00622
CCN1	ENST00000968417.1		c.277+50G>C	intron	N/A	ENSP00000638476.1
CCN1	ENST00000866036.1		c.277+50G>C	intron	N/A	ENSP00000536095.1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23771

AN:

152102

Hom.:

2269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0510

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.187

GnomAD2 exomes

AF:

0.189

AC:

41387

AN:

219016

AF XY:

0.188

show subpopulations

Gnomad AFR exome

AF:

0.0484

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.189

Gnomad EAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.197

AC:

279502

AN:

1421246

Hom.:

28441

Cov.:

AF XY:

0.196

AC XY:

137958

AN XY:

704206

show subpopulations

African (AFR)

AF:

0.0448

AC:

1452

AN:

32408

American (AMR)

AF:

0.248

AC:

10102

AN:

40802

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

4571

AN:

25294

East Asian (EAS)

AF:

0.143

AC:

5579

AN:

38906

South Asian (SAS)

AF:

0.160

AC:

13412

AN:

83616

European-Finnish (FIN)

AF:

0.161

AC:

8367

AN:

51902

Middle Eastern (MID)

AF:

0.226

AC:

1263

AN:

5578

European-Non Finnish (NFE)

AF:

0.206

AC:

223750

AN:

1084064

Other (OTH)

AF:

0.188

AC:

11006

AN:

58676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

11726

23453

35179

46906

58632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7788

15576

23364

31152

38940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.156

AC:

23762

AN:

152220

Hom.:

2266

Cov.:

AF XY:

0.155

AC XY:

11523

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0509

AC:

2115

AN:

41550

American (AMR)

AF:

0.207

AC:

3165

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

631

AN:

3468

East Asian (EAS)

AF:

0.138

AC:

717

AN:

5184

South Asian (SAS)

AF:

0.154

AC:

742

AN:

4822

European-Finnish (FIN)

AF:

0.163

AC:

1727

AN:

10586

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.205

AC:

13947

AN:

67988

Other (OTH)

AF:

0.188

AC:

396

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

994

1989

2983

3978

4972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.179

Hom.:

505

Bravo

AF:

0.161

Asia WGS

AF:

0.112

AC:

390

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

4.1

Mutation Taster

=55/45

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over