11-116820912-C-CTCCTGCTGCTGT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000482.4(APOA4):c.1145_1146insACAGCAGCAGGA(p.Gln384_Gln387dup) variant causes a 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. 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 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.0880

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 1578213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOA4	NM_000482.4	c.1145_1146insACAGCAGCAGGA	p.Gln384_Gln387dup	inframe_insertion	3/3	ENST00000357780.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA4	ENST00000357780.5	c.1145_1146insACAGCAGCAGGA	p.Gln384_Gln387dup	inframe_insertion	3/3	1	NM_000482.4	P1
	ENST00000645414.1	n.169-99_169-88dup		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.00104 AC: 261 AN: 251184 Hom.: 1 AF XY: 0.000707 AC XY: 96 AN XY: 135802

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.0147

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.000878

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

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00238

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 20, 2023

- -

APOLIPOPROTEIN A-IV RARE VARIANT, APOA4*0 Other:1

other, no assertion criteria provided

literature only

OMIM

Dec 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs539176882; hg19: chr11-116691628;