Genetic Variant 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCN3	NM_002514.4 link	c.*440C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000259526.4	NP_002505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCN3	ENST00000259526.4 link	c.*440C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_002514.4	ENSP00000259526.3
ENSG00000253398	ENST00000519786.1 link	n.191-3528G>A		intron_variant	Intron 3 of 3	3

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over