11-116822748-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000482.4(APOA4):c.87G>A(p.Thr29=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.66

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]

ACMG classification

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	UniProt
APOA4	NM_000482.4	c.87G>A	p.Thr29=	synonymous_variant	2/3	ENST00000357780.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA4	ENST00000357780.5	c.87G>A	p.Thr29=	synonymous_variant	2/3	1	NM_000482.4	P1

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122711 AN: 152100 Hom.: 49848 Cov.: 33

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

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.: 66 AF XY: 0.807 AC XY: 586990 AN XY: 727220

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.: 33 AF XY: 0.795 AC XY: 59139 AN XY: 74412

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	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

Other links and lift over

dbSNP: rs5092; hg19: chr11-116693464; COSMIC: COSV63359985; COSMIC: COSV63359985;