dbSNP rs2071518: CCN3:c.*440C>T (chr8-119423572-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002514.4(CCN3):c.*440C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 153,434 control chromosomes in the GnomAD database, including 10,055 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 0.33 ( 10009 hom., cov: 32)

Exomes 𝑓: 0.23 ( 46 hom. )

Consequence

CCN3
NM_002514.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

51 publications found

Variant links:

Genes affected

CCN3 (HGNC:7885): (cellular communication network factor 3) The protein encoded by this gene is a small secreted cysteine-rich protein and a member of the CCN family of regulatory proteins. CNN family proteins associate with the extracellular matrix and play an important role in cardiovascular and skeletal development, fibrosis and cancer development. [provided by RefSeq, Feb 2009]

CCN3 links:

ENSG00000253398 (HGNC:):

ENSG00000253398 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002514.4. 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
	CCN3	NM_002514.4	MANE Select	c.*440C>T		3_prime_UTR	Exon 5 of 5	NP_002505.1	P48745

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCN3	ENST00000259526.4	TSL:1 MANE Select	c.*440C>T	3_prime_UTR	Exon 5 of 5	ENSP00000259526.3	P48745
CCN3	ENST00000864983.1		c.*440C>T	3_prime_UTR	Exon 5 of 5	ENSP00000535042.1
CCN3	ENST00000960553.1		c.*440C>T	3_prime_UTR	Exon 4 of 4	ENSP00000630612.1

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50526

AN:

151952

Hom.:

9968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.550

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.337

GnomAD4 exome

AF:

0.235

AC:

320

AN:

1364

Hom.:

Cov.:

AF XY:

0.233

AC XY:

159

AN XY:

682

show subpopulations

African (AFR)

AF:

0.591

AC:

AN:

American (AMR)

AF:

0.180

AC:

AN:

206

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

AN:

East Asian (EAS)

AF:

0.136

AC:

AN:

South Asian (SAS)

AF:

0.231

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.225

AC:

202

AN:

896

Other (OTH)

AF:

0.350

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.333

AC:

50606

AN:

152070

Hom.:

10009

Cov.:

AF XY:

0.326

AC XY:

24270

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.551

AC:

22830

AN:

41444

American (AMR)

AF:

0.232

AC:

3538

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1295

AN:

3464

East Asian (EAS)

AF:

0.151

AC:

781

AN:

5176

South Asian (SAS)

AF:

0.318

AC:

1535

AN:

4826

European-Finnish (FIN)

AF:

0.183

AC:

1934

AN:

10580

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.259

AC:

17604

AN:

67984

Other (OTH)

AF:

0.335

AC:

707

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1590

3179

4769

6358

7948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.287

Hom.:

23916

Bravo

AF:

0.345

Asia WGS

AF:

0.266

AC:

926

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.4

(source)

DANN

Benign

0.26

PhyloP100

1.9

Mutation Taster

=100/0

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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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