Variant 6-112054441-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_198239.2(CCN6):c.48+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,601,226 control chromosomes in the GnomAD database, including 52,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 4688 hom., cov: 30)

Exomes 𝑓: 0.25 ( 48275 hom. )

Consequence

CCN6
NM_198239.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.30

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:

CCN6 (HGNC:):

CCN6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 6-112054441-G-A is Benign according to our data. Variant chr6-112054441-G-A is described in ClinVar as [Benign]. Clinvar id is 1264724.Status of the report is criteria_provided_single_submitter, 1 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	Protein	UniProt
CCN6	NM_198239.2 linkuse as main transcript	c.48+36G>A		intron_variant		ENST00000368666.7	NP_937882.2	O95389-1A0A384NYW3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCN6	ENST00000368666.7 linkuse as main transcript	c.48+36G>A		intron_variant		1	NM_198239.2	ENSP00000357655.4		O95389-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37535

AN:

151474

Hom.:

4689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.234

AC:

58490

AN:

249780

Hom.:

7289

AF XY:

0.231

AC XY:

31280

AN XY:

135150

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.293

Gnomad EAS exome

AF:

0.329

Gnomad SAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.254

AC:

368788

AN:

1449634

Hom.:

48275

Cov.:

AF XY:

0.251

AC XY:

181010

AN XY:

721958

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.309

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.248

AC:

37548

AN:

151592

Hom.:

4688

Cov.:

AF XY:

0.242

AC XY:

17926

AN XY:

74070

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.321

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.259

Hom.:

1148

Bravo

AF:

0.252

Asia WGS

AF:

0.230

AC:

799

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.46

DANN

Benign

0.56

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