19-8369301-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1
The NM_139314.3(ANGPTL4):c.630G>A(p.Pro210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00615 in 1,611,874 control chromosomes in the GnomAD database, including 464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.030 ( 236 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 228 hom. )
Consequence
ANGPTL4
NM_139314.3 synonymous
NM_139314.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.982
Genes affected
ANGPTL4 (HGNC:16039): (angiopoietin like 4) This gene encodes a glycosylated, secreted protein containing a C-terminal fibrinogen domain. The encoded protein is induced by peroxisome proliferation activators and functions as a serum hormone that regulates glucose homeostasis, lipid metabolism, and insulin sensitivity. This protein can also act as an apoptosis survival factor for vascular endothelial cells and can prevent metastasis by inhibiting vascular growth and tumor cell invasion. The C-terminal domain may be proteolytically-cleaved from the full-length secreted protein. Decreased expression of this gene has been associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. This gene was previously referred to as ANGPTL2 but has been renamed ANGPTL4. [provided by RefSeq, Sep 2013]
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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=-0.85).
BP6
Variant 19-8369301-G-A is Benign according to our data. Variant chr19-8369301-G-A is described in ClinVar as [Benign]. Clinvar id is 3041796.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.982 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANGPTL4 | NM_139314.3 | c.630G>A | p.Pro210= | synonymous_variant | 4/7 | ENST00000301455.7 | NP_647475.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANGPTL4 | ENST00000301455.7 | c.630G>A | p.Pro210= | synonymous_variant | 4/7 | 1 | NM_139314.3 | ENSP00000301455 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0304 AC: 4614AN: 151968Hom.: 235 Cov.: 32
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GnomAD3 exomes AF: 0.00870 AC: 2147AN: 246880Hom.: 95 AF XY: 0.00703 AC XY: 935AN XY: 133034
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GnomAD4 exome AF: 0.00362 AC: 5282AN: 1459788Hom.: 228 Cov.: 31 AF XY: 0.00338 AC XY: 2454AN XY: 725904
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GnomAD4 genome AF: 0.0304 AC: 4627AN: 152086Hom.: 236 Cov.: 32 AF XY: 0.0297 AC XY: 2211AN XY: 74362
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
ANGPTL4-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 26, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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