rs61747644

Variant names:

• chr8-143213279-C-T
• rs61747644
• NM_178172.6:c.12C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143213279-C-T
• chr8-143213279-C-A
• chr8-143213279-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.02
• Publications: 11 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1287705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPIHBP1	NM_178172.6	MANE Select	c.12C>T	p.Leu4Leu	synonymous	Exon 1 of 4	NP_835466.2	Q8IV16
	GPIHBP1	NM_001301772.2		c.12C>T	p.Leu4Leu	synonymous	Exon 1 of 5	NP_001288701.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPIHBP1	ENST00000622500.2	TSL:1 MANE Select	c.12C>T	p.Leu4Leu	synonymous	Exon 1 of 4	ENSP00000480053.1	Q8IV16
	GPIHBP1	ENST00000852007.1		c.12C>T	p.Leu4Leu	synonymous	Exon 1 of 5	ENSP00000522066.1
	GPIHBP1	ENST00000852008.1		c.12C>T	p.Leu4Leu	synonymous	Exon 1 of 4	ENSP00000522067.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22923 AN: 152012 Hom.: 2091 Cov.: 33

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

GnomAD2 exomes AF: 0.182 AC: 40211 AN: 220506 AF XY: 0.181

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 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.: 31 AF XY: 0.182 AC XY: 130682 AN XY: 716480

African (AFR) AF: 0.0452 AC: 1511 AN: 33432

American (AMR) AF: 0.213 AC: 8899 AN: 41698

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3818 AN: 25726

East Asian (EAS) AF: 0.192 AC: 7533 AN: 39146

South Asian (SAS) AF: 0.162 AC: 13530 AN: 83326

European-Finnish (FIN) AF: 0.245 AC: 11531 AN: 47088

Middle Eastern (MID) AF: 0.163 AC: 940 AN: 5750

European-Non Finnish (NFE) AF: 0.185 AC: 205016 AN: 1106730

Other (OTH) AF: 0.175 AC: 10473 AN: 59900

GnomAD4 genome AF: 0.151 AC: 22918 AN: 152130 Hom.: 2089 Cov.: 33 AF XY: 0.154 AC XY: 11449 AN XY: 74366

African (AFR) AF: 0.0493 AC: 2047 AN: 41534

American (AMR) AF: 0.183 AC: 2803 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3466

East Asian (EAS) AF: 0.185 AC: 953 AN: 5156

South Asian (SAS) AF: 0.157 AC: 760 AN: 4828

European-Finnish (FIN) AF: 0.244 AC: 2584 AN: 10588

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12655 AN: 67958

Other (OTH) AF: 0.145 AC: 305 AN: 2106

Alfa AF: 0.157 Hom.: 651

Bravo AF: 0.142

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.57
PhyloP100		-4.0
PromoterAI		-0.0044	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61747644; hg19: chr8-144295154; COSMIC: COSV58209070;