rs5090

Positions:

• chr11-116823339-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The 11-116823339-C-G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 943,090 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (172 hom., cov: 33)
  • Exomes 𝑓: 0.048 (1159 hom.)
• Consequence: APOA4 NM_000482.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.470

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-116823339-C-G is Benign according to our data. Variant chr11-116823339-C-G is described in ClinVar as [Benign]. Clinvar id is 1286717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA4	NM_000482.4			upstream_gene_variant		ENST00000357780.5	NP_000473.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOA4	ENST00000357780.5			upstream_gene_variant		1	NM_000482.4	ENSP00000350425	P1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5977 AN: 152204 Hom.: 172 Cov.: 33

Gnomad AFR AF: 0.00967

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0481 AC: 38008 AN: 790768 Hom.: 1159 Cov.: 10 AF XY: 0.0471 AC XY: 19623 AN XY: 416796

Gnomad4 AFR exome AF: 0.00865

Gnomad4 AMR exome AF: 0.0244

Gnomad4 ASJ exome AF: 0.0448

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.0138

Gnomad4 FIN exome AF: 0.0604

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.0461

GnomAD4 genome AF: 0.0392 AC: 5977 AN: 152322 Hom.: 172 Cov.: 33 AF XY: 0.0385 AC XY: 2868 AN XY: 74484

Gnomad4 AFR AF: 0.00964

Gnomad4 AMR AF: 0.0304

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0585

Gnomad4 NFE AF: 0.0615

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0507 Hom.: 21

Bravo AF: 0.0352

Asia WGS AF: 0.00664 AC: 23 AN: 3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5090; hg19: chr11-116694055; COSMIC: COSV63360462;