rs11538389

Positions:

• chr8-143213308-T-G

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.41T>G​(p.Phe14Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 1,595,946 control chromosomes in the GnomAD database, including 640,974 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.89 (60546 hom., cov: 32)
  • Exomes 𝑓: 0.90 (580428 hom.)
• Consequence: GPIHBP1 NM_178172.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176

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 (MetaRNN=0.0046406984).
• BP6: Variant 8-143213308-T-G is Benign according to our data. Variant chr8-143213308-T-G is described in ClinVar as [Benign]. Clinvar id is 769221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPIHBP1	NM_178172.6	c.41T>G	p.Phe14Cys	missense_variant	1/4	ENST00000622500.2	NP_835466.2
GPIHBP1	NM_001301772.2	c.41T>G	p.Phe14Cys	missense_variant	1/5		NP_001288701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPIHBP1	ENST00000622500.2	c.41T>G	p.Phe14Cys	missense_variant	1/4	1	NM_178172.6	ENSP00000480053	P1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135494 AN: 152060 Hom.: 60501 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.898

GnomAD4 exome AF: 0.896 AC: 1292910 AN: 1443768 Hom.: 580428 Cov.: 47 AF XY: 0.894 AC XY: 641095 AN XY: 717260

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.859

Gnomad4 ASJ exome AF: 0.936

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.829

Gnomad4 FIN exome AF: 0.884

Gnomad4 NFE exome AF: 0.909

Gnomad4 OTH exome AF: 0.889

GnomAD4 genome AF: 0.891 AC: 135594 AN: 152178 Hom.: 60546 Cov.: 32 AF XY: 0.885 AC XY: 65834 AN XY: 74388

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.912

Gnomad4 OTH AF: 0.893

Alfa AF: 0.907 Hom.: 67370

Bravo AF: 0.892

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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.1
MetaRNN	Benign	0.0046	T
Sift4G	Benign	1.0	T
Vest4		0.24
gMVP		0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11538389; hg19: chr8-144295183;