rs7103224

Variant names:

• chr11-116793250-G-A
• rs7103224
• ENST00000873023.1:c.-471C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-116793250-G-A
• chr11-116793250-G-C

Variant summary

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

The ENST00000873023.1(APOA5):​c.-471C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 152,018 control chromosomes in the GnomAD database, including 470 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 0.060 (470 hom., cov: 32)
• Consequence: APOA5 ENST00000873023.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 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.-471C>T		upstream_gene	N/A	ENSP00000543082.1

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9171 AN: 151900 Hom.: 471 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0714

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0550

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

GnomAD4 genome AF: 0.0602 AC: 9158 AN: 152018 Hom.: 470 Cov.: 32 AF XY: 0.0640 AC XY: 4755 AN XY: 74288

African (AFR) AF: 0.0145 AC: 602 AN: 41476

American (AMR) AF: 0.0401 AC: 612 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3472

East Asian (EAS) AF: 0.0715 AC: 369 AN: 5158

South Asian (SAS) AF: 0.218 AC: 1047 AN: 4806

European-Finnish (FIN) AF: 0.100 AC: 1056 AN: 10538

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5155 AN: 67980

Other (OTH) AF: 0.0539 AC: 114 AN: 2114

Alfa AF: 0.0630 Hom.: 42

Bravo AF: 0.0511

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.84
DANN	Benign	0.58
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs7103224; hg19: chr11-116663966;