chr6-35231868-A-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_152753.4(SCUBE3):c.469+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,601,864 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.014 ( 61 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 37 hom. )
Consequence
SCUBE3
NM_152753.4 intron
NM_152753.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.69
Genes affected
SCUBE3 (HGNC:13655): (signal peptide, CUB domain and EGF like domain containing 3) This gene encodes a member of the signal peptide, complement subcomponents C1r/C1s, Uegf, bone morphogenetic protein-1 and epidermal growth factor-like domain containing protein family. Overexpression of this gene in human embryonic kidney cells results in secretion of a glycosylated form of the protein that forms oligomers and tethers to the cell surface. This gene is upregulated in lung cancer tumor tissue compared to healthy tissue and is associated with loss of the epithelial marker E-cadherin and with increased expression of vimentin, a mesenchymal marker. In addition, the protein encoded by this gene is a transforming growth factor beta receptor ligand, and when secreted by cancer cells, it can be cleaved in vitro to release the N-terminal epidermal growth factor-like repeat domain and the C-terminal complement subcomponents C1r/C1s domain. Both the full length protein and C-terminal fragment can bind to the transforming growth factor beta type II receptor to promote the epithelial-mesenchymal transition and tumor angiogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
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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=-0.66).
BP6
Variant 6-35231868-A-G is Benign according to our data. Variant chr6-35231868-A-G is described in ClinVar as [Benign]. Clinvar id is 716891.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2130/152190) while in subpopulation AFR AF= 0.0478 (1985/41524). AF 95% confidence interval is 0.0461. There are 61 homozygotes in gnomad4. There are 1011 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 61 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCUBE3 | NM_152753.4 | c.469+9A>G | intron_variant | ENST00000274938.8 | |||
SCUBE3-AS1 | XR_001744102.2 | n.321-388T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCUBE3 | ENST00000274938.8 | c.469+9A>G | intron_variant | 1 | NM_152753.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0140 AC: 2127AN: 152072Hom.: 62 Cov.: 32
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GnomAD3 exomes AF: 0.00403 AC: 998AN: 247876Hom.: 26 AF XY: 0.00296 AC XY: 397AN XY: 134028
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GnomAD4 exome AF: 0.00165 AC: 2388AN: 1449674Hom.: 37 Cov.: 31 AF XY: 0.00144 AC XY: 1036AN XY: 719204
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GnomAD4 genome AF: 0.0140 AC: 2130AN: 152190Hom.: 61 Cov.: 32 AF XY: 0.0136 AC XY: 1011AN XY: 74416
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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 | Jul 18, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at