11-116822748-C-T

Variant names:

• chr11-116822748-C-T
• rs5092
• NM_000482.4:c.87G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000482.4(APOA4):​c.87G>A​(p.Thr29Thr) 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:3
• Conservation: PhyloP100: -2.66
• Publications: 38 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]

ENSG00000305923 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.87G>A	p.Thr29Thr	synonymous	Exon 2 of 3	NP_000473.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA4	ENST00000357780.5	TSL:1 MANE Select	c.87G>A	p.Thr29Thr	synonymous	Exon 2 of 3	ENSP00000350425.3
	ENSG00000305923	ENST00000814126.1		n.136-5417C>T		intron	N/A

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

GnomAD2 exomes AF: 0.771 AC: 193783 AN: 251450 AF XY: 0.766

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 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

African (AFR) AF: 0.852 AC: 28519 AN: 33478

American (AMR) AF: 0.743 AC: 33237 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 20175 AN: 26136

East Asian (EAS) AF: 0.611 AC: 24273 AN: 39698

South Asian (SAS) AF: 0.634 AC: 54682 AN: 86258

European-Finnish (FIN) AF: 0.734 AC: 39209 AN: 53392

Middle Eastern (MID) AF: 0.813 AC: 4692 AN: 5768

European-Non Finnish (NFE) AF: 0.841 AC: 934886 AN: 1111992

Other (OTH) AF: 0.802 AC: 48458 AN: 60394

GnomAD4 genome AF: 0.807 AC: 122797 AN: 152218 Hom.: 49879 Cov.: 33 AF XY: 0.795 AC XY: 59139 AN XY: 74412

African (AFR) AF: 0.853 AC: 35424 AN: 41550

American (AMR) AF: 0.750 AC: 11474 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2717 AN: 3470

East Asian (EAS) AF: 0.616 AC: 3186 AN: 5170

South Asian (SAS) AF: 0.617 AC: 2972 AN: 4820

European-Finnish (FIN) AF: 0.722 AC: 7638 AN: 10584

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56590 AN: 68010

Other (OTH) AF: 0.804 AC: 1699 AN: 2112

Alfa AF: 0.825 Hom.: 92727

Bravo AF: 0.818

Asia WGS AF: 0.624 AC: 2174 AN: 3478

EpiCase AF: 0.834

EpiControl AF: 0.839

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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