chr11-116820912-C-CTCCTGCTGCTGT

Variant names:

• chr11-116820912-C-CTCCTGCTGCTGT
• rs539176882
• NM_000482.4:c.1134_1145dupACAGCAGCAGGA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000482.4(APOA4):​c.1134_1145dupACAGCAGCAGGA​(p.Glu382_Gln383insGlnGlnGlnGlu) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000789 in 1,613,920 control chromosomes in the GnomAD database, including 12 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (5 hom.)
• Consequence: APOA4 NM_000482.4 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.0880
• Publications: 0 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 -6 ACMG points.

• BP6: Variant 11-116820912-C-CTCCTGCTGCTGT is Benign according to our data. Variant chr11-116820912-C-CTCCTGCTGCTGT is described in ClinVar as Benign. ClinVar VariationId is 1578213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.1134_1145dupACAGCAGCAGGA	p.Glu382_Gln383insGlnGlnGlnGlu	disruptive_inframe_insertion	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.1134_1145dupACAGCAGCAGGA	p.Glu382_Gln383insGlnGlnGlnGlu	disruptive_inframe_insertion	Exon 3 of 3	ENSP00000350425.3	P06727
	ENSG00000285513	ENST00000645414.1		n.169-99_169-88dupCTGTTCCTGCTG		intron	N/A
	ENSG00000305923	ENST00000814126.1		n.135+6581_135+6592dupCTGTTCCTGCTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 670 AN: 152106 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00104 AC: 261 AN: 251184 AF XY: 0.000707

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.000695

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000410 AC: 600 AN: 1461704 Hom.: 5 Cov.: 66 AF XY: 0.000344 AC XY: 250 AN XY: 727164

African (AFR) AF: 0.0147 AC: 490 AN: 33408

American (AMR) AF: 0.000850 AC: 38 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5762

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111934

Other (OTH) AF: 0.000878 AC: 53 AN: 60388

GnomAD4 genome AF: 0.00442 AC: 673 AN: 152216 Hom.: 7 Cov.: 33 AF XY: 0.00441 AC XY: 328 AN XY: 74426

African (AFR) AF: 0.0153 AC: 636 AN: 41504

American (AMR) AF: 0.00183 AC: 28 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68022

Other (OTH) AF: 0.00238 AC: 5 AN: 2102

Alfa AF: 0.000131 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	APOLIPOPROTEIN A-IV RARE VARIANT, APOA4*0 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.088
Mutation Taster		=81/19	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs539176882; hg19: chr11-116691628;