Variant 6-112054104-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198239.2(CCN6):c.-254A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 648,812 control chromosomes in the GnomAD database, including 21,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4905 hom., cov: 31)

Exomes 𝑓: 0.25 ( 16274 hom. )

Consequence

CCN6
NM_198239.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.34

Variant links:

Genes affected

CCN6 (HGNC:12771): (cellular communication network factor 6) This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like domain. This gene is overexpressed in colon tumors. It may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. Mutations of this gene are associated with progressive pseudorheumatoid dysplasia, an autosomal recessive skeletal disorder, indicating that the gene is essential for normal postnatal skeletal growth and cartilage homeostasis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CCN6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-112054104-A-G is Benign according to our data. Variant chr6-112054104-A-G is described in ClinVar as [Benign]. Clinvar id is 355054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCN6	NM_198239.2 linkuse as main transcript	c.-254A>G		5_prime_UTR_variant	1/5	ENST00000368666.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCN6	ENST00000368666.7 linkuse as main transcript	c.-254A>G		5_prime_UTR_variant	1/5	1	NM_198239.2	P1	O95389-1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38402

AN:

151818

Hom.:

4905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.266

GnomAD4 exome

AF:

0.249

AC:

123554

AN:

496878

Hom.:

16274

Cov.:

AF XY:

0.243

AC XY:

64401

AN XY:

265460

show subpopulations

Gnomad4 AFR exome

AF:

0.248

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.253

AC:

38416

AN:

151934

Hom.:

4905

Cov.:

AF XY:

0.248

AC XY:

18405

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.212

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.321

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.259

Hom.:

1777

Bravo

AF:

0.257

Asia WGS

AF:

0.232

AC:

805

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Progressive pseudorheumatoid dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.6

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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