Variant 11-116822748-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000482.4(APOA4):c.87G>A(p.Thr29Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,614,058 control chromosomes in the GnomAD database, including 536,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 49879 hom., cov: 33)

Exomes 𝑓: 0.81 ( 486403 hom. )

Consequence

APOA4
NM_000482.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.66

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-116822748-C-T is Benign according to our data. Variant chr11-116822748-C-T is described in ClinVar as [Benign]. Clinvar id is 1287091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.66 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA4	NM_000482.4 linkuse as main transcript	c.87G>A	p.Thr29Thr	synonymous_variant	2/3	ENST00000357780.5	NP_000473.2	P06727

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOA4	ENST00000357780.5 linkuse as main transcript	c.87G>A	p.Thr29Thr	synonymous_variant	2/3	1	NM_000482.4	ENSP00000350425.3		P06727

Frequencies

GnomAD3 genomes

AF:

0.807

AC:

122711

AN:

152100

Hom.:

49848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.853

Gnomad AMI

AF:

0.939

Gnomad AMR

AF:

0.750

Gnomad ASJ

AF:

0.783

Gnomad EAS

AF:

0.616

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.722

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.808

GnomAD3 exomes

AF:

0.771

AC:

193783

AN:

251450

Hom.:

75652

AF XY:

0.766

AC XY:

104167

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.853

Gnomad AMR exome

AF:

0.742

Gnomad ASJ exome

AF:

0.774

Gnomad EAS exome

AF:

0.624

Gnomad SAS exome

AF:

0.633

Gnomad FIN exome

AF:

0.731

Gnomad NFE exome

AF:

0.835

Gnomad OTH exome

AF:

0.788

GnomAD4 exome

AF:

0.813

AC:

1188131

AN:

1461840

Hom.:

486403

Cov.:

AF XY:

0.807

AC XY:

586990

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.852

Gnomad4 AMR exome

AF:

0.743

Gnomad4 ASJ exome

AF:

0.772

Gnomad4 EAS exome

AF:

0.611

Gnomad4 SAS exome

AF:

0.634

Gnomad4 FIN exome

AF:

0.734

Gnomad4 NFE exome

AF:

0.841

Gnomad4 OTH exome

AF:

0.802

GnomAD4 genome

AF:

0.807

AC:

122797

AN:

152218

Hom.:

49879

Cov.:

AF XY:

0.795

AC XY:

59139

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.853

Gnomad4 AMR

AF:

0.750

Gnomad4 ASJ

AF:

0.783

Gnomad4 EAS

AF:

0.616

Gnomad4 SAS

AF:

0.617

Gnomad4 FIN

AF:

0.722

Gnomad4 NFE

AF:

0.832

Gnomad4 OTH

AF:

0.804

Alfa

AF:

0.823

Hom.:

19570

Bravo

AF:

0.818

Asia WGS

AF:

0.624

AC:

2174

AN:

3478

EpiCase

AF:

0.834

EpiControl

AF:

0.839

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.4

DANN

Benign

0.48

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