8-133213091-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_003882.4(CCN4):c.297C>T(p.Leu99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,614,040 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0035 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 0 hom. )
Consequence
CCN4
NM_003882.4 synonymous
NM_003882.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.221
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 8-133213091-C-T is Benign according to our data. Variant chr8-133213091-C-T is described in ClinVar as [Benign]. Clinvar id is 783535.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.221 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCN4 | NM_003882.4 | c.297C>T | p.Leu99= | synonymous_variant | 2/5 | ENST00000250160.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCN4 | ENST00000250160.11 | c.297C>T | p.Leu99= | synonymous_variant | 2/5 | 1 | NM_003882.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00348 AC: 529AN: 152194Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00100 AC: 252AN: 251048Hom.: 1 AF XY: 0.000751 AC XY: 102AN XY: 135816
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GnomAD4 exome AF: 0.000318 AC: 465AN: 1461728Hom.: 0 Cov.: 35 AF XY: 0.000276 AC XY: 201AN XY: 727150
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GnomAD4 genome AF: 0.00349 AC: 532AN: 152312Hom.: 5 Cov.: 32 AF XY: 0.00361 AC XY: 269AN XY: 74470
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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 | Invitae | Feb 26, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at