rs5090

Variant names:

• chr11-116823339-C-G
• rs5090
• ENST00000814126.1:n.136-4826C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000814126.1(ENSG00000305923):​n.136-4826C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 943,090 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (172 hom., cov: 33)
  • Exomes 𝑓: 0.048 (1159 hom.)
• Consequence: ENSG00000305923 ENST00000814126.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.470
• Publications: 8 publications found

Genes affected

ENSG00000305923 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-116823339-C-G is Benign according to our data. Variant chr11-116823339-C-G is described in ClinVar as Benign. ClinVar VariationId is 1286717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000814126.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA4	NM_000482.4	MANE Select	c.-148G>C		upstream_gene	N/A	NP_000473.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000305923	ENST00000814126.1		n.136-4826C>G		intron	N/A
	APOA4	ENST00000357780.5	TSL:1 MANE Select	c.-148G>C		upstream_gene	N/A	ENSP00000350425.3

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5977 AN: 152204 Hom.: 172 Cov.: 33

Gnomad AFR AF: 0.00967

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0481 AC: 38008 AN: 790768 Hom.: 1159 Cov.: 10 AF XY: 0.0471 AC XY: 19623 AN XY: 416796

African (AFR) AF: 0.00865 AC: 179 AN: 20702

American (AMR) AF: 0.0244 AC: 985 AN: 40444

Ashkenazi Jewish (ASJ) AF: 0.0448 AC: 946 AN: 21102

East Asian (EAS) AF: 0.0000278 AC: 1 AN: 35938

South Asian (SAS) AF: 0.0138 AC: 975 AN: 70498

European-Finnish (FIN) AF: 0.0604 AC: 2821 AN: 46688

Middle Eastern (MID) AF: 0.0341 AC: 115 AN: 3376

European-Non Finnish (NFE) AF: 0.0588 AC: 30237 AN: 514062

Other (OTH) AF: 0.0461 AC: 1749 AN: 37958

GnomAD4 genome AF: 0.0392 AC: 5977 AN: 152322 Hom.: 172 Cov.: 33 AF XY: 0.0385 AC XY: 2868 AN XY: 74484

African (AFR) AF: 0.00964 AC: 401 AN: 41582

American (AMR) AF: 0.0304 AC: 465 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4832

European-Finnish (FIN) AF: 0.0585 AC: 621 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0615 AC: 4180 AN: 68022

Other (OTH) AF: 0.0303 AC: 64 AN: 2114

Alfa AF: 0.0507 Hom.: 21

Bravo AF: 0.0352

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.62
PhyloP100		0.47
PromoterAI		0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5090; hg19: chr11-116694055; COSMIC: COSV63360462;