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rs11672433

chr19-8373832-G-Achr19-8373832-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_139314.3(ANGPTL4):c.1167G>A(p.Pro389=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,613,792 control chromosomes in the GnomAD database, including 14,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.096 ( 960 hom., cov: 32)
Exomes 𝑓: 0.13 ( 13918 hom. )

Consequence

ANGPTL4
NM_139314.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.08
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-8373832-G-A is Benign according to our data. Variant chr19-8373832-G-A is described in ClinVar as [Benign]. Clinvar id is 3056777.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.08 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANGPTL4NM_139314.3 linkuse as main transcriptc.1167G>A p.Pro389= synonymous_variant 7/7 ENST00000301455.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANGPTL4ENST00000301455.7 linkuse as main transcriptc.1167G>A p.Pro389= synonymous_variant 7/71 NM_139314.3 P1Q9BY76-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0959
AC:
14595
AN:
152132
Hom.:
960
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0257
Gnomad AMI
AF:
0.173
Gnomad AMR
AF:
0.0798
Gnomad ASJ
AF:
0.0956
Gnomad EAS
AF:
0.000772
Gnomad SAS
AF:
0.0904
Gnomad FIN
AF:
0.0989
Gnomad MID
AF:
0.168
Gnomad NFE
AF:
0.148
Gnomad OTH
AF:
0.101
GnomAD3 exomes
AF:
0.102
AC:
25700
AN:
251108
Hom.:
1734
AF XY:
0.106
AC XY:
14438
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.0239
Gnomad AMR exome
AF:
0.0570
Gnomad ASJ exome
AF:
0.0999
Gnomad EAS exome
AF:
0.000490
Gnomad SAS exome
AF:
0.0966
Gnomad FIN exome
AF:
0.0983
Gnomad NFE exome
AF:
0.146
Gnomad OTH exome
AF:
0.116
GnomAD4 exome
AF:
0.132
AC:
192252
AN:
1461542
Hom.:
13918
Cov.:
32
AF XY:
0.131
AC XY:
95507
AN XY:
727078
show subpopulations
Gnomad4 AFR exome
AF:
0.0229
Gnomad4 AMR exome
AF:
0.0586
Gnomad4 ASJ exome
AF:
0.0984
Gnomad4 EAS exome
AF:
0.000479
Gnomad4 SAS exome
AF:
0.0977
Gnomad4 FIN exome
AF:
0.0995
Gnomad4 NFE exome
AF:
0.148
Gnomad4 OTH exome
AF:
0.115
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0958
AC:
14587
AN:
152250
Hom.:
960
Cov.:
32
AF XY:
0.0938
AC XY:
6986
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0256
Gnomad4 AMR
AF:
0.0796
Gnomad4 ASJ
AF:
0.0956
Gnomad4 EAS
AF:
0.000774
Gnomad4 SAS
AF:
0.0909
Gnomad4 FIN
AF:
0.0989
Gnomad4 NFE
AF:
0.148
Gnomad4 OTH
AF:
0.100
Alfa
AF:
0.135
Hom.:
2165
Bravo
AF:
0.0895
Asia WGS
AF:
0.0350
AC:
122
AN:
3478
EpiCase
AF:
0.140
EpiControl
AF:
0.145

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

ANGPTL4-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 21, 2019This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
0.067
Dann
Benign
0.62
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11672433; hg19: chr19-8438716; API