11-116820918-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000482.4(APOA4):c.1140G>T(p.Gln380His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 1,614,064 control chromosomes in the GnomAD database, including 4,952 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 306 hom., cov: 33)

Exomes 𝑓: 0.075 ( 4646 hom. )

Consequence

APOA4
NM_000482.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:3

Conservation

PhyloP100: -0.513

Variant links:

Genes affected

APOA4 (HGNC:602): (apolipoprotein A4) Apoliprotein (apo) A-IV gene contains 3 exons separated by two introns. A sequence polymorphism has been identified in the 3'UTR of the third exon. The primary translation product is a 396-residue preprotein which after proteolytic processing is secreted its primary site of synthesis, the intestine, in association with chylomicron particles. Although its precise function is not known, apo A-IV is a potent activator of lecithin-cholesterol acyltransferase in vitro. [provided by RefSeq, Jul 2008]

APOA4 links:

ENSG00000285513 (HGNC:):

ENSG00000285513 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017547011).

BP6

Variant 11-116820918-C-A is Benign according to our data. Variant chr11-116820918-C-A is described in ClinVar as [Benign]. Clinvar id is 17905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA4	NM_000482.4 link	c.1140G>T	p.Gln380His	missense_variant	Exon 3 of 3	ENST00000357780.5	NP_000473.2	P06727

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA4	ENST00000357780.5 link	c.1140G>T	p.Gln380His	missense_variant	Exon 3 of 3	1	NM_000482.4	ENSP00000350425.3		P06727
ENSG00000285513	ENST00000645414.1 link	n.169-102C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7905

AN:

152210

Hom.:

306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0500

Gnomad ASJ

AF:

0.0628

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0809

Gnomad OTH

AF:

0.0516

GnomAD3 exomes

AF:

0.0523

AC:

13128

AN:

251086

Hom.:

470

AF XY:

0.0528

AC XY:

7162

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.0361

Gnomad ASJ exome

AF:

0.0665

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0188

Gnomad FIN exome

AF:

0.0516

Gnomad NFE exome

AF:

0.0784

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.0752

AC:

109875

AN:

1461736

Hom.:

4646

Cov.:

AF XY:

0.0730

AC XY:

53054

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0119

Gnomad4 AMR exome

AF:

0.0383

Gnomad4 ASJ exome

AF:

0.0665

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0192

Gnomad4 FIN exome

AF:

0.0513

Gnomad4 NFE exome

AF:

0.0878

Gnomad4 OTH exome

AF:

0.0651

GnomAD4 genome

AF:

0.0519

AC:

7904

AN:

152328

Hom.:

306

Cov.:

AF XY:

0.0483

AC XY:

3600

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.0500

Gnomad4 ASJ

AF:

0.0628

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.0488

Gnomad4 NFE

AF:

0.0809

Gnomad4 OTH

AF:

0.0510

Alfa

AF:

0.0701

Hom.:

920

Bravo

AF:

0.0523

TwinsUK

AF:

0.0876

AC:

325

ALSPAC

AF:

0.0944

AC:

364

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.0829

AC:

712

ExAC

AF:

0.0524

AC:

6357

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0775

EpiControl

AF:

0.0772

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 02, 2025

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

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 9714133, 20117098, 1349197) -

APOLIPOPROTEIN A-IV POLYMORPHISM, APOA4*1/APOA4*2

Pathogenic:1

May 01, 1992

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.24

DANN

Benign

0.58

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.017

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.17

REVEL

Benign

0.047

Sift

Benign

0.45

Sift4G

Benign

0.19

Vest4

0.051

MutPred

0.25

Loss of solvent accessibility (P = 0.0635);

MPC

0.050

ClinPred

0.00085

GERP RS

0.14

gMVP

0.20

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