11-116820959-T-G

Variant names:

• chr11-116820959-T-G
• rs675
• NM_000482.4:c.1099A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000482.4(APOA4):​c.1099A>C​(p.Thr367Pro) variant causes a missense 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. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T367A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: APOA4 NM_000482.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 69 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]

ENSG00000285513 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022464305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA4	NM_000482.4	c.1099A>C	p.Thr367Pro	missense_variant	Exon 3 of 3	ENST00000357780.5	NP_000473.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA4	ENST00000357780.5	c.1099A>C	p.Thr367Pro	missense_variant	Exon 3 of 3	1	NM_000482.4	ENSP00000350425.3
ENSG00000285513	ENST00000645414.1	n.169-61T>G		intron_variant	Intron 1 of 1
ENSG00000305923	ENST00000814126.1	n.135+6619T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.5
DANN	Benign	0.22
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0015	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.21
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.083
Sift	Benign	0.87	T
Sift4G	Benign	0.16	T
Vest4		0.062
MutPred		0.14		Loss of phosphorylation at T367 (P = 0.0247);
MVP		0.12
MPC		0.063
ClinPred		0.045	T
GERP RS		0.012
gMVP		0.070
Mutation Taster		=96/4	polymorphism

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: rs675; hg19: chr11-116691675;