Variant 8-143213279-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178172.6(GPIHBP1):c.12C>T(p.Leu4Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,594,926 control chromosomes in the GnomAD database, including 27,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2089 hom., cov: 33)

Exomes 𝑓: 0.18 ( 25048 hom. )

Consequence

GPIHBP1
NM_178172.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.02

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 8-143213279-C-T is Benign according to our data. Variant chr8-143213279-C-T is described in ClinVar as [Benign]. Clinvar id is 1287705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-143213279-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPIHBP1	NM_178172.6 linkuse as main transcript	c.12C>T	p.Leu4Leu	synonymous_variant	1/4	ENST00000622500.2	NP_835466.2	Q8IV16
GPIHBP1	NM_001301772.2 linkuse as main transcript	c.12C>T	p.Leu4Leu	synonymous_variant	1/5		NP_001288701.1	Q8IV16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPIHBP1	ENST00000622500.2 linkuse as main transcript	c.12C>T	p.Leu4Leu	synonymous_variant	1/4	1	NM_178172.6	ENSP00000480053.1		Q8IV16

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22923

AN:

152012

Hom.:

2091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0494

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.183

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

GnomAD3 exomes

AF:

0.182

AC:

40211

AN:

220506

Hom.:

3874

AF XY:

0.181

AC XY:

21656

AN XY:

119352

show subpopulations

Gnomad AFR exome

AF:

0.0463

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.182

AC:

263251

AN:

1442796

Hom.:

25048

Cov.:

AF XY:

0.182

AC XY:

130682

AN XY:

716480

show subpopulations

Gnomad4 AFR exome

AF:

0.0452

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.245

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.151

AC:

22918

AN:

152130

Hom.:

2089

Cov.:

AF XY:

0.154

AC XY:

11449

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0493

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.244

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.159

Hom.:

650

Bravo

AF:

0.142

Asia WGS

AF:

0.174

AC:

603

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2019

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.7

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over