19-8371316-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139314.3(ANGPTL4):c.833G>A(p.Arg278Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,613,846 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 89 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 115 hom. )

Consequence

ANGPTL4
NM_139314.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.51

Publications

15 publications found

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:

RAB11B-AS1 (HGNC:44178): (RAB11B antisense RNA 1)

RAB11B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005083561).

BP6

Variant 19-8371316-G-A is Benign according to our data. Variant chr19-8371316-G-A is described in ClinVar as [Benign]. Clinvar id is 768962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL4	NM_139314.3 link	c.833G>A	p.Arg278Gln	missense_variant	Exon 6 of 7	ENST00000301455.7	NP_647475.1	Q9BY76-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPTL4	ENST00000301455.7 link	c.833G>A	p.Arg278Gln	missense_variant	Exon 6 of 7	1	NM_139314.3	ENSP00000301455.1		Q9BY76-1

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2817

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0611

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00751

AC:

1882

AN:

250742

AF XY:

0.00680

show subpopulations

Gnomad AFR exome

AF:

0.0620

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0173

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00298

AC:

4358

AN:

1461552

Hom.:

115

Cov.:

AF XY:

0.00315

AC XY:

2294

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.0655

AC:

2192

AN:

33480

American (AMR)

AF:

0.00302

AC:

135

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00821

AC:

326

AN:

39700

South Asian (SAS)

AF:

0.0134

AC:

1158

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53106

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000147

AC:

164

AN:

1112000

Other (OTH)

AF:

0.00585

AC:

353

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

319

637

956

1274

1593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0186

AC:

2832

AN:

152294

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1334

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0613

AC:

2549

AN:

41558

American (AMR)

AF:

0.00523

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0184

AC:

AN:

5172

South Asian (SAS)

AF:

0.0139

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68012

Other (OTH)

AF:

0.0109

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

138

276

414

552

690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00693

Hom.:

Bravo

AF:

0.0213

ESP6500AA

AF:

0.0570

AC:

251

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00859

AC:

1043

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.7

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.026

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.56

.;T

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

N;.

PhyloP100

1.5

PrimateAI

Benign

0.20

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.12

Sift

Benign

0.98

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.017

B;.

Vest4

0.058

MVP

0.60

MPC

0.23

ClinPred

0.0029

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.20

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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19-8371316-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over