rs17120035

Variant names:

• chr11-116793135-C-T
• rs17120035
• ENST00000873023.1:c.-356G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000873023.1(APOA5):​c.-356G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 152,282 control chromosomes in the GnomAD database, including 497 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.066 (497 hom., cov: 32)
• Consequence: APOA5 ENST00000873023.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 15 publications found

Genes affected

APOA5 (HGNC:17288): (apolipoprotein A5) The protein encoded by this gene is an apolipoprotein that plays an important role in regulating the plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of high density lipoprotein and is highly similar to a rat protein that is upregulated in response to liver injury. Mutations in this gene have been associated with hypertriglyceridemia and hyperlipoproteinemia type 5. This gene is located proximal to the apolipoprotein gene cluster on chromosome 11q23. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Oct 2009]

APOA5 Gene-Disease associations (from GenCC):

• hypertriglyceridemia 1

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• hyperlipoproteinemia type V

  Inheritance: AD, SD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000873023.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA5	ENST00000873023.1		c.-356G>A		upstream_gene	N/A	ENSP00000543082.1

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10105 AN: 152164 Hom.: 498 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0491

Gnomad EAS AF: 0.0715

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0564

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0663 AC: 10093 AN: 152282 Hom.: 497 Cov.: 32 AF XY: 0.0698 AC XY: 5196 AN XY: 74446

African (AFR) AF: 0.0353 AC: 1466 AN: 41574

American (AMR) AF: 0.0438 AC: 670 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0491 AC: 170 AN: 3464

East Asian (EAS) AF: 0.0717 AC: 372 AN: 5190

South Asian (SAS) AF: 0.217 AC: 1048 AN: 4826

European-Finnish (FIN) AF: 0.0997 AC: 1056 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0759 AC: 5161 AN: 68014

Other (OTH) AF: 0.0553 AC: 117 AN: 2116

Alfa AF: 0.0698 Hom.: 941

Bravo AF: 0.0579

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.80
PhyloP100		0.0090

Splicing

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

Other links and lift over

dbSNP: rs17120035; hg19: chr11-116663851;