Variant 19-8371404-C-T 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.921C>T(p.Pro307Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 1,613,432 control chromosomes in the GnomAD database, including 619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.035 ( 318 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 301 hom. )

Consequence

ANGPTL4
NM_139314.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.10

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 19-8371404-C-T is Benign according to our data. Variant chr19-8371404-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042332.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL4	NM_139314.3 link	c.921C>T	p.Pro307Pro	synonymous_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.921C>T	p.Pro307Pro	synonymous_variant	Exon 6 of 7	1	NM_139314.3	ENSP00000301455.1		Q9BY76-1

Frequencies

GnomAD3 genomes

AF:

0.0349

AC:

5315

AN:

152192

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0248

GnomAD3 exomes

AF:

0.00902

AC:

2248

AN:

249214

Hom.:

133

AF XY:

0.00681

AC XY:

921

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.00527

Gnomad ASJ exome

AF:

0.00260

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.000473

Gnomad OTH exome

AF:

0.00509

GnomAD4 exome

AF:

0.00380

AC:

5552

AN:

1461122

Hom.:

301

Cov.:

AF XY:

0.00334

AC XY:

2426

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.00637

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000948

Gnomad4 NFE exome

AF:

0.000265

Gnomad4 OTH exome

AF:

0.00785

GnomAD4 genome

AF:

0.0350

AC:

5330

AN:

152310

Hom.:

318

Cov.:

AF XY:

0.0343

AC XY:

2552

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.00995

Hom.:

Bravo

AF:

0.0398

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000711

ClinVar

Significance: Likely 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: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

-0.67

CADD

Benign

0.14

DANN

Benign

0.71

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