6-112054441-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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]

ACMG classification

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	UniProt
CCN6	NM_198239.2	c.48+36G>A		intron_variant		ENST00000368666.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCN6	ENST00000368666.7	c.48+36G>A		intron_variant		1	NM_198239.2	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37535 AN: 151474 Hom.: 4689 Cov.: 30

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

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.: 27 AF XY: 0.251 AC XY: 181010 AN XY: 721958

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.: 30 AF XY: 0.242 AC XY: 17926 AN XY: 74070

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 18, 2021

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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

Other links and lift over

dbSNP: rs2280153; hg19: chr6-112375644;