rs116843064

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_139314.3(ANGPTL4):c.118G>A(p.Glu40Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0171 in 1,555,220 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars). Synonymous variant affecting the same amino acid position (i.e. E40E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.015 ( 30 hom., cov: 32)

Exomes 𝑓: 0.017 ( 232 hom. )

Consequence

ANGPTL4
NM_139314.3 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 6.58

Publications

183 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040303767).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.015 (2292/152350) while in subpopulation AMR AF = 0.0236 (361/15308). AF 95% confidence interval is 0.0216. There are 30 homozygotes in GnomAd4. There are 1095 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL4	NM_139314.3 link	c.118G>A	p.Glu40Lys	missense_variant	Exon 1 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.118G>A	p.Glu40Lys	missense_variant	Exon 1 of 7	1	NM_139314.3	ENSP00000301455.1		Q9BY76-1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2292

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00294

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.0186

GnomAD2 exomes

AF:

0.0133

AC:

2016

AN:

151260

AF XY:

0.0130

show subpopulations

Gnomad AFR exome

AF:

0.00316

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0257

Gnomad NFE exome

AF:

0.0201

Gnomad OTH exome

AF:

0.0175

GnomAD4 exome

AF:

0.0174

AC:

24354

AN:

1402870

Hom.:

232

Cov.:

AF XY:

0.0171

AC XY:

11879

AN XY:

693090

show subpopulations

African (AFR)

AF:

0.00272

AC:

AN:

32338

American (AMR)

AF:

0.0129

AC:

471

AN:

36488

Ashkenazi Jewish (ASJ)

AF:

0.0154

AC:

389

AN:

25214

East Asian (EAS)

AF:

0.00

AC:

AN:

36776

South Asian (SAS)

AF:

0.000763

AC:

AN:

79906

European-Finnish (FIN)

AF:

0.0260

AC:

1156

AN:

44394

Middle Eastern (MID)

AF:

0.000746

AC:

AN:

5360

European-Non Finnish (NFE)

AF:

0.0196

AC:

21244

AN:

1084120

Other (OTH)

AF:

0.0161

AC:

941

AN:

58274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1601

3202

4804

6405

8006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

768

1536

2304

3072

3840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0150

AC:

2292

AN:

152350

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1095

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00293

AC:

122

AN:

41584

American (AMR)

AF:

0.0236

AC:

361

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0254

AC:

270

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0207

AC:

1405

AN:

68034

Other (OTH)

AF:

0.0184

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

121

241

362

482

603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0183

Hom.:

Bravo

AF:

0.0146

ESP6500AA

AF:

0.000953

AC:

ESP6500EA

AF:

0.0160

AC:

132

ExAC

AF:

0.00807

AC:

918

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Plasma triglyceride level quantitative trait locus

Other:1

May 08, 2009

OMIM

Significance:association

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

.;.;T;T;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.96

D;D;D;.;D

MetaRNN

Benign

0.0040

T;T;T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.7

.;.;.;M;M

PhyloP100

6.6

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.1

.;.;.;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.010

.;.;.;D;D

Sift4G

Uncertain

0.012

D;D;D;D;D

Polyphen

1.0

.;.;.;D;.

Vest4

0.39, 0.34

MPC

0.81

ClinPred

0.036

GERP RS

5.0

PromoterAI

0.047

Neutral

(source)

Varity_R

0.30

gMVP

0.73

Mutation Taster

=201/99

polymorphism

(source)

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

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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