rs72691625

Variant names:

• chr8-143212799-G-A
• rs72691625
• ENST00000852007.1:c.-469G>A

Variant summary

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

The ENST00000852007.1(GPIHBP1):​c.-469G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,260 control chromosomes in the GnomAD database, including 2,090 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 0.15 (2090 hom., cov: 33)
• Consequence: GPIHBP1 ENST00000852007.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 5 publications found

Genes affected

GPIHBP1 (HGNC:24945): (glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1) This gene encodes a capillary endothelial cell protein that facilitates the lipolytic processing of triglyceride-rich lipoproteins. The encoded protein is a glycosylphosphatidylinositol-anchored protein that is a member of the lymphocyte antigen 6 (Ly6) family. This protein plays a major role in transporting lipoprotein lipase (LPL) from the subendothelial spaces to the capillary lumen. Mutations in this gene are the cause of hyperlipoproteinemia, type 1D. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

GPIHBP1 Gene-Disease associations (from GenCC):

• hyperlipoproteinemia, type 1D

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000852007.1. 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
	GPIHBP1	ENST00000852007.1		c.-469G>A		upstream_gene	N/A	ENSP00000522066.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22954 AN: 152142 Hom.: 2092 Cov.: 33

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.151 AC: 22949 AN: 152260 Hom.: 2090 Cov.: 33 AF XY: 0.154 AC XY: 11459 AN XY: 74432

African (AFR) AF: 0.0494 AC: 2055 AN: 41574

American (AMR) AF: 0.184 AC: 2811 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3472

East Asian (EAS) AF: 0.185 AC: 957 AN: 5178

South Asian (SAS) AF: 0.157 AC: 759 AN: 4830

European-Finnish (FIN) AF: 0.244 AC: 2586 AN: 10602

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12666 AN: 67990

Other (OTH) AF: 0.145 AC: 306 AN: 2112

Alfa AF: 0.171 Hom.: 531

Bravo AF: 0.142

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.76
PhyloP100		-0.30
PromoterAI		-0.027	Neutral

Splicing

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

Other links and lift over

dbSNP: rs72691625; hg19: chr8-144294674;