rs16893344

Variant names:

• chr8-133194036-C-T
• rs16893344
• NM_003882.4:c.69+2823C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003882.4(CCN4):​c.69+2823C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,080 control chromosomes in the GnomAD database, including 7,101 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 0.29 (7101 hom., cov: 32)
• Consequence: CCN4 NM_003882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 22 publications found

Genes affected

CCN4 (HGNC:12769): (cellular communication network factor 4) 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 may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. It is expressed at a high level in fibroblast cells, and overexpressed in colon tumors. The encoded protein binds to decorin and biglycan, two members of a family of small leucine-rich proteoglycans present in the extracellular matrix of connective tissue, and possibly prevents the inhibitory activity of decorin and biglycan in tumor cell proliferation. It also attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase. It is 83% identical to the mouse protein at the amino acid level. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003882.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCN4	NM_003882.4	MANE Select	c.69+2823C>T		intron	N/A	NP_003873.1
	CCN4	NM_080838.3		c.69+2823C>T		intron	N/A	NP_543028.1
	CCN4	NM_001204869.2		c.69+2823C>T		intron	N/A	NP_001191798.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCN4	ENST00000250160.11	TSL:1 MANE Select	c.69+2823C>T		intron	N/A	ENSP00000250160.5
	CCN4	ENST00000220856.6	TSL:1	c.69+2823C>T		intron	N/A	ENSP00000220856.6
	CCN4	ENST00000517423.5	TSL:1	c.69+2823C>T		intron	N/A	ENSP00000427744.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43570 AN: 151962 Hom.: 7101 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43580 AN: 152080 Hom.: 7101 Cov.: 32 AF XY: 0.290 AC XY: 21523 AN XY: 74322

African (AFR) AF: 0.167 AC: 6919 AN: 41494

American (AMR) AF: 0.235 AC: 3586 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3468

East Asian (EAS) AF: 0.141 AC: 731 AN: 5170

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4826

European-Finnish (FIN) AF: 0.440 AC: 4633 AN: 10538

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24289 AN: 67976

Other (OTH) AF: 0.255 AC: 539 AN: 2114

Alfa AF: 0.328 Hom.: 36347

Bravo AF: 0.262

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.76
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16893344; hg19: chr8-134206279;