11-116820795-GGACAGACA-GGACA

Variant names:

• chr11-116820795-GGACA-G
• rs2234669
• NM_000482.4:c.*68_*71delTGTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000482.4(APOA4):​c.*68_*71delTGTC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,577,418 control chromosomes in the GnomAD database, including 197,947 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (13398 hom., cov: 0)
  • Exomes 𝑓: 0.50 (184549 hom.)
• Consequence: APOA4 NM_000482.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.937
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-116820795-GGACA-G is Benign according to our data. Variant chr11-116820795-GGACA-G is described in ClinVar as Benign. ClinVar VariationId is 1238294.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 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.*68_*71delTGTC		3_prime_UTR	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.*68_*71delTGTC		3_prime_UTR	Exon 3 of 3	ENSP00000350425.3	P06727
	ENSG00000285513	ENST00000645414.1		n.165_168delACAG		splice_region non_coding_transcript_exon	Exon 1 of 2
	ENSG00000305923	ENST00000814126.1		n.135+6469_135+6472delACAG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58724 AN: 151762 Hom.: 13406 Cov.: 0

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.500 AC: 712397 AN: 1425540 Hom.: 184549 AF XY: 0.494 AC XY: 348997 AN XY: 705810

African (AFR) AF: 0.122 AC: 4011 AN: 32758

American (AMR) AF: 0.473 AC: 20073 AN: 42396

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 9804 AN: 23874

East Asian (EAS) AF: 0.270 AC: 10661 AN: 39414

South Asian (SAS) AF: 0.319 AC: 25812 AN: 80896

European-Finnish (FIN) AF: 0.467 AC: 21964 AN: 47056

Middle Eastern (MID) AF: 0.346 AC: 1490 AN: 4312

European-Non Finnish (NFE) AF: 0.540 AC: 591478 AN: 1095972

Other (OTH) AF: 0.460 AC: 27104 AN: 58862

GnomAD4 genome AF: 0.387 AC: 58715 AN: 151878 Hom.: 13398 Cov.: 0 AF XY: 0.381 AC XY: 28251 AN XY: 74240

African (AFR) AF: 0.141 AC: 5838 AN: 41500

American (AMR) AF: 0.433 AC: 6604 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1411 AN: 3464

East Asian (EAS) AF: 0.292 AC: 1503 AN: 5150

South Asian (SAS) AF: 0.312 AC: 1503 AN: 4814

European-Finnish (FIN) AF: 0.457 AC: 4818 AN: 10548

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35511 AN: 67832

Other (OTH) AF: 0.404 AC: 852 AN: 2110

Alfa AF: 0.313 Hom.: 889

Bravo AF: 0.382

Asia WGS AF: 0.276 AC: 963 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2234669; hg19: chr11-116691511; COSMIC: COSV63359960;