Variant 8-119416576-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002514.4(CCN3):c.44G>T(p.Cys15Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,614,040 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 11 hom. )

Consequence

CCN3
NM_002514.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.560

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:

CCN3 (HGNC:):

CCN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003968537).

BP6

Variant 8-119416576-G-T is Benign according to our data. Variant chr8-119416576-G-T is described in ClinVar as [Benign]. Clinvar id is 775267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00635 (967/152360) while in subpopulation AFR AF= 0.0175 (727/41586). AF 95% confidence interval is 0.0164. There are 7 homozygotes in gnomad4. There are 462 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCN3	NM_002514.4 linkuse as main transcript	c.44G>T	p.Cys15Phe	missense_variant	1/5	ENST00000259526.4	NP_002505.1	P48745A0A024R9J4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCN3	ENST00000259526.4 linkuse as main transcript	c.44G>T	p.Cys15Phe	missense_variant	1/5	1	NM_002514.4	ENSP00000259526.3	P48745
CCN3	ENST00000520082.1 linkuse as main transcript	n.127G>T		non_coding_transcript_exon_variant	1/2	2
ENSG00000286282	ENST00000670132.1 linkuse as main transcript	n.264+108C>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00634

AC:

965

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00334

AC:

836

AN:

250006

Hom.:

AF XY:

0.00272

AC XY:

368

AN XY:

135198

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.00394

Gnomad ASJ exome

AF:

0.0232

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00170

AC:

2482

AN:

1461680

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1226

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.00374

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000732

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00635

AC:

967

AN:

152360

Hom.:

Cov.:

AF XY:

0.00620

AC XY:

462

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.00713

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00335

AC:

407

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Benign

0.057

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.2

REVEL

Benign

0.22

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.010

Vest4

0.37

MVP

0.70

MPC

0.39

ClinPred

0.029

GERP RS

3.5

gMVP

0.51

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