rs1729411

Variant names:

• chr11-116792959-G-A
• rs1729411
• ENST00000873023.1:c.-180C>T

Variant summary

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

The ENST00000873023.1(APOA5):​c.-180C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 152,210 control chromosomes in the GnomAD database, including 819 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 0.091 (819 hom., cov: 32)
• Consequence: APOA5 ENST00000873023.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 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.-180C>T		5_prime_UTR	Exon 1 of 4	ENSP00000543082.1
	APOA5	ENST00000873021.1		c.-295C>T		upstream_gene	N/A	ENSP00000543080.1

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13793 AN: 152092 Hom.: 820 Cov.: 32

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0906 AC: 13792 AN: 152210 Hom.: 819 Cov.: 32 AF XY: 0.0882 AC XY: 6565 AN XY: 74404

African (AFR) AF: 0.0278 AC: 1155 AN: 41536

American (AMR) AF: 0.0804 AC: 1229 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4818

European-Finnish (FIN) AF: 0.128 AC: 1352 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9124 AN: 68010

Other (OTH) AF: 0.105 AC: 221 AN: 2114

Alfa AF: 0.111 Hom.: 311

Bravo AF: 0.0852

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.5
DANN	Benign	0.79
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs1729411; hg19: chr11-116663675;