8-143215153-T-C

Position:

• chr8-143215153-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178172.6(GPIHBP1):​c.295+27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 1,610,008 control chromosomes in the GnomAD database, including 646,223 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 0.89 (60487 hom., cov: 34)
  • Exomes 𝑓: 0.90 (585736 hom.)
• Consequence: GPIHBP1 NM_178172.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPIHBP1	NM_178172.6	c.295+27T>C		intron_variant		ENST00000622500.2	NP_835466.2
GPIHBP1	NM_001301772.2	c.295+27T>C		intron_variant			NP_001288701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPIHBP1	ENST00000622500.2	c.295+27T>C		intron_variant		1	NM_178172.6	ENSP00000480053	P1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135421 AN: 152066 Hom.: 60442 Cov.: 34

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.899

GnomAD4 exome AF: 0.895 AC: 1305080 AN: 1457824 Hom.: 585736 Cov.: 40 AF XY: 0.894 AC XY: 648148 AN XY: 725386

Gnomad4 AFR exome AF: 0.892

Gnomad4 AMR exome AF: 0.857

Gnomad4 ASJ exome AF: 0.936

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.829

Gnomad4 FIN exome AF: 0.883

Gnomad4 NFE exome AF: 0.909

Gnomad4 OTH exome AF: 0.888

GnomAD4 genome AF: 0.891 AC: 135521 AN: 152184 Hom.: 60487 Cov.: 34 AF XY: 0.884 AC XY: 65792 AN XY: 74396

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.893

Alfa AF: 0.908 Hom.: 10641

Bravo AF: 0.891

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.5

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56046179; hg19: chr8-144297028;