8-143213459-G-A

Position:

• chr8-143213459-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_178172.6(GPIHBP1):​c.52+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 767,380 control chromosomes in the GnomAD database, including 5,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (933 hom., cov: 30)
  • Exomes 𝑓: 0.11 (4560 hom.)
• Consequence: GPIHBP1 NM_178172.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-143213459-G-A is Benign according to our data. Variant chr8-143213459-G-A is described in ClinVar as [Benign]. Clinvar id is 1273383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-143213459-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPIHBP1	NM_178172.6	c.52+140G>A		intron_variant		ENST00000622500.2	NP_835466.2
GPIHBP1	NM_001301772.2	c.52+140G>A		intron_variant			NP_001288701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPIHBP1	ENST00000622500.2	c.52+140G>A		intron_variant		1	NM_178172.6	ENSP00000480053.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15723 AN: 151784 Hom.: 933 Cov.: 30

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0977

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0601

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0609

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.115 AC: 70555 AN: 615474 Hom.: 4560 AF XY: 0.116 AC XY: 37282 AN XY: 322674

Gnomad4 AFR exome AF: 0.0512

Gnomad4 AMR exome AF: 0.0989

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.0404

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.104 AC: 15728 AN: 151906 Hom.: 933 Cov.: 30 AF XY: 0.106 AC XY: 7871 AN XY: 74232

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.0975

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0601

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.108

Alfa AF: 0.130 Hom.: 194

Bravo AF: 0.0950

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs74880494; hg19: chr8-144295334;