Variant 19-8373832-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_139314.3(ANGPTL4):c.1167G>A(p.Pro389Pro) 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 (no stars).

Frequency

Genomes: 𝑓 0.096 ( 960 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13918 hom. )

Consequence

ANGPTL4
NM_139314.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided 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]

ANGPTL4 links:

ANGPTL4 (HGNC:):

ANGPTL4 links:

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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=-0.84).

BP6

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 no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-4.08 with no splicing effect.

BA1

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	Protein	UniProt
ANGPTL4	NM_139314.3 linkuse as main transcript	c.1167G>A	p.Pro389Pro	synonymous_variant	7/7	ENST00000301455.7	NP_647475.1	Q9BY76-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPTL4	ENST00000301455.7 linkuse as main transcript	c.1167G>A	p.Pro389Pro	synonymous_variant	7/7	1	NM_139314.3	ENSP00000301455.1		Q9BY76-1

Frequencies

GnomAD3 genomes

AF:

0.0959

AC:

14595

AN:

152132

Hom.:

960

Cov.:

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.:

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

AF:

0.0958

AC:

14587

AN:

152250

Hom.:

960

Cov.:

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: 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

Oct 21, 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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over