Variant rs1044250 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_139314.3(ANGPTL4):c.797C>T(p.Thr266Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,613,680 control chromosomes in the GnomAD database, including 76,738 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6532 hom., cov: 32)

Exomes 𝑓: 0.31 ( 70206 hom. )

Consequence

ANGPTL4
NM_139314.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.785

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002986014).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPTL4	NM_139314.3 linkuse as main transcript	c.797C>T	p.Thr266Met	missense_variant	6/7	ENST00000301455.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPTL4	ENST00000301455.7 linkuse as main transcript	c.797C>T	p.Thr266Met	missense_variant	6/7	1	NM_139314.3	P1	Q9BY76-1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43773

AN:

151934

Hom.:

6530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.0678

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.304

AC:

76257

AN:

250634

Hom.:

12666

AF XY:

0.301

AC XY:

40793

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.238

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.363

Gnomad EAS exome

AF:

0.0497

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.398

Gnomad NFE exome

AF:

0.318

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.306

AC:

446549

AN:

1461628

Hom.:

70206

Cov.:

AF XY:

0.304

AC XY:

220896

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.370

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.0993

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.392

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.288

AC:

43796

AN:

152052

Hom.:

6532

Cov.:

AF XY:

0.288

AC XY:

21408

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.314

Gnomad4 ASJ

AF:

0.362

Gnomad4 EAS

AF:

0.0684

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.393

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.300

Hom.:

17941

Bravo

AF:

0.282

TwinsUK

AF:

0.319

AC:

1181

ALSPAC

AF:

0.289

AC:

1112

ESP6500AA

AF:

0.255

AC:

1123

ESP6500EA

AF:

0.310

AC:

2667

ExAC

AF:

0.303

AC:

36765

Asia WGS

AF:

0.176

AC:

614

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

Cadd

Benign

7.6

Dann

Benign

0.95

DEOGEN2

Uncertain

0.44

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.086

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.5

H;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.070

Sift

Benign

0.21

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.13

B;.

Vest4

0.078

MPC

0.22

ClinPred

0.044

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.72

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over