11-116821050-C-T

Variant names:

• chr11-116821050-C-T
• rs5109
• NM_000482.4:c.1008G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000482.4(APOA4):​c.1008G>A​(p.Val336Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V336V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: APOA4 NM_000482.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant medullary cystic kidney disease with or without hyperuricemia

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000285513 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.703 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000482.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA4	NM_000482.4	MANE Select	c.1008G>A	p.Val336Val	synonymous	Exon 3 of 3	NP_000473.2	P06727

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA4	ENST00000357780.5	TSL:1 MANE Select	c.1008G>A	p.Val336Val	synonymous	Exon 3 of 3	ENSP00000350425.3	P06727
	ENSG00000285513	ENST00000645414.1		n.199C>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000305923	ENST00000814126.1		n.135+6710C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 87

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 22

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.5
DANN	Benign	0.70
PhyloP100		0.70

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

Other links and lift over

dbSNP: rs5109; hg19: chr11-116691766;