Genetic Variant GPIHBP1:c.295+27T>C (chr8-143215153-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.111

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

hyperlipoproteinemia, type 1D
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

GPIHBP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178172.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPIHBP1	NM_178172.6	MANE Select	c.295+27T>C		intron	N/A	NP_835466.2
	GPIHBP1	NM_001301772.2		c.295+27T>C		intron	N/A	NP_001288701.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPIHBP1	ENST00000622500.2	TSL:1 MANE Select	c.295+27T>C		intron	N/A	ENSP00000480053.1

Frequencies

GnomAD3 genomes

AF:

0.891

AC:

135421

AN:

152066

Hom.:

60442

Cov.:

show subpopulations

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.:

AF XY:

0.894

AC XY:

648148

AN XY:

725386

show subpopulations

African (AFR)

AF:

0.892

AC:

29829

AN:

33436

American (AMR)

AF:

0.857

AC:

38285

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.936

AC:

24419

AN:

26098

East Asian (EAS)

AF:

0.684

AC:

27142

AN:

39672

South Asian (SAS)

AF:

0.829

AC:

71460

AN:

86206

European-Finnish (FIN)

AF:

0.883

AC:

46017

AN:

52134

Middle Eastern (MID)

AF:

0.929

AC:

5354

AN:

5766

European-Non Finnish (NFE)

AF:

0.909

AC:

1009028

AN:

1109536

Other (OTH)

AF:

0.888

AC:

53546

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

8985

17970

26954

35939

44924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21380

42760

64140

85520

106900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.891

AC:

135521

AN:

152184

Hom.:

60487

Cov.:

AF XY:

0.884

AC XY:

65792

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.888

AC:

36865

AN:

41518

American (AMR)

AF:

0.872

AC:

13351

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.937

AC:

3252

AN:

3470

East Asian (EAS)

AF:

0.704

AC:

3615

AN:

5136

South Asian (SAS)

AF:

0.822

AC:

3965

AN:

4824

European-Finnish (FIN)

AF:

0.883

AC:

9373

AN:

10616

Middle Eastern (MID)

AF:

0.918

AC:

270

AN:

294

European-Non Finnish (NFE)

AF:

0.913

AC:

62058

AN:

67996

Other (OTH)

AF:

0.893

AC:

1888

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

788

1577

2365

3154

3942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.908

Hom.:

10641

Bravo

AF:

0.891

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

2.5

(source)

PhyloP100

-0.11

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over