Genetic Variant ANGPTL4:p.Pro210Pro (chr19-8369301-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_139314.3(ANGPTL4):c.630G>A(p.Pro210Pro) 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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.982

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANGPTL4	NM_139314.3 link	c.630G>A	p.Pro210Pro	synonymous_variant	Exon 4 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.630G>A	p.Pro210Pro	synonymous_variant	Exon 4 of 7	1	NM_139314.3	ENSP00000301455.1		Q9BY76-1

Frequencies

GnomAD3 genomes

AF:

0.0304

AC:

4614

AN:

151968

Hom.:

235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00994

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0215

GnomAD2 exomes

AF:

0.00870

AC:

2147

AN:

246880

AF XY:

0.00703

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000296

Gnomad OTH exome

AF:

0.00371

GnomAD4 exome

AF:

0.00362

AC:

5282

AN:

1459788

Hom.:

228

Cov.:

AF XY:

0.00338

AC XY:

2454

AN XY:

725904

show subpopulations

African (AFR)

AF:

0.111

AC:

3720

AN:

33454

American (AMR)

AF:

0.00563

AC:

251

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25882

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39686

South Asian (SAS)

AF:

0.00832

AC:

711

AN:

85476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00853

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

0.000142

AC:

158

AN:

1111644

Other (OTH)

AF:

0.00654

AC:

394

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

263

526

790

1053

1316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0304

AC:

4627

AN:

152086

Hom.:

236

Cov.:

AF XY:

0.0297

AC XY:

2211

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.105

AC:

4356

AN:

41454

American (AMR)

AF:

0.0100

AC:

153

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00974

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

67996

Other (OTH)

AF:

0.0213

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

205

410

616

821

1026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0291

Hom.:

156

Bravo

AF:

0.0342

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ANGPTL4-related disorder

Benign:1

Nov 26, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.85

CADD

Benign

0.37

(source)

DANN

Benign

0.33

PhyloP100

-0.98

Mutation Taster

=100/0

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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19-8369301-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