11-116821050-C-A

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.1008G>T(p.Val336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,614,188 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (102 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (121 hom.)
• Consequence: APOA4 NM_000482.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.703

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 11-116821050-C-A is Benign according to our data. Variant chr11-116821050-C-A is described in ClinVar as [Benign]. Clinvar id is 788568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.703 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOA4	NM_000482.4	c.1008G>T	p.Val336=	synonymous_variant	3/3	ENST00000357780.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA4	ENST00000357780.5	c.1008G>T	p.Val336=	synonymous_variant	3/3	1	NM_000482.4	P1
	ENST00000645414.1	n.199C>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3389 AN: 152200 Hom.: 102 Cov.: 34

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00994

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00544 AC: 1367 AN: 251480 Hom.: 40 AF XY: 0.00365 AC XY: 496 AN XY: 135916

Gnomad AFR exome AF: 0.0749

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00220 AC: 3220 AN: 1461870 Hom.: 121 Cov.: 87 AF XY: 0.00189 AC XY: 1371 AN XY: 727234

Gnomad4 AFR exome AF: 0.0763

Gnomad4 AMR exome AF: 0.00402

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000908

Gnomad4 OTH exome AF: 0.00573

GnomAD4 genome AF: 0.0224 AC: 3410 AN: 152318 Hom.: 102 Cov.: 34 AF XY: 0.0219 AC XY: 1629 AN XY: 74492

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.00999

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00744 Hom.: 17

Bravo AF: 0.0248

Asia WGS AF: 0.00664 AC: 24 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	8.9
Dann	Benign	0.69

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: rs5109; hg19: chr11-116691766;