chr15-55340661-G-T

Position:

chr15-55340661-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004855.5(PIGB):c.896G>T(p.Trp299Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,610,638 control chromosomes in the GnomAD database, including 124,295 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 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 0.48 ( 21134 hom., cov: 30)

Exomes 𝑓: 0.36 ( 103161 hom. )

Consequence

PIGB
NM_004855.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.04

Variant links:

Genes affected

PIGB (HGNC:8959): (phosphatidylinositol glycan anchor biosynthesis class B) This gene encodes a transmembrane protein that is located in the endoplasmic reticulum and is involved in GPI-anchor biosynthesis. The glycosylphosphatidylinositol (GPI) anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene is thought to encode a member of a family of dolichol-phosphate-mannose (Dol-P-Man) dependent mannosyltransferases. [provided by RefSeq, Jul 2008]

PIGB links:

CCPG1 (HGNC:24227): (cell cycle progression 1) Involved in positive regulation of cell cycle and positive regulation of cell population proliferation. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCPG1 links:

PIGB (HGNC:):

PIGB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.996635E-6).

BP6

Variant 15-55340661-G-T is Benign according to our data. Variant chr15-55340661-G-T is described in ClinVar as [Benign]. Clinvar id is 1179234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGB	NM_004855.5 linkuse as main transcript	c.896G>T	p.Trp299Leu	missense_variant	8/12	ENST00000164305.10	NP_004846.4	Q92521

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGB	ENST00000164305.10 linkuse as main transcript	c.896G>T	p.Trp299Leu	missense_variant	8/12	1	NM_004855.5	ENSP00000164305.5		Q92521

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73362

AN:

151560

Hom.:

21084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.746

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.445

GnomAD3 exomes

AF:

0.408

AC:

100268

AN:

246016

Hom.:

23463

AF XY:

0.397

AC XY:

52966

AN XY:

133358

show subpopulations

Gnomad AFR exome

AF:

0.793

Gnomad AMR exome

AF:

0.426

Gnomad ASJ exome

AF:

0.355

Gnomad EAS exome

AF:

0.770

Gnomad SAS exome

AF:

0.410

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.318

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.361

AC:

526556

AN:

1458960

Hom.:

103161

Cov.:

AF XY:

0.360

AC XY:

260936

AN XY:

725560

show subpopulations

Gnomad4 AFR exome

AF:

0.801

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.739

Gnomad4 SAS exome

AF:

0.406

Gnomad4 FIN exome

AF:

0.295

Gnomad4 NFE exome

AF:

0.329

Gnomad4 OTH exome

AF:

0.397

GnomAD4 genome

AF:

0.484

AC:

73467

AN:

151678

Hom.:

21134

Cov.:

AF XY:

0.481

AC XY:

35648

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.791

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.365

Gnomad4 EAS

AF:

0.746

Gnomad4 SAS

AF:

0.425

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.445

Alfa

AF:

0.367

Hom.:

27777

Bravo

AF:

0.509

TwinsUK

AF:

0.338

AC:

1253

ALSPAC

AF:

0.335

AC:

1293

ESP6500AA

AF:

0.766

AC:

2869

ESP6500EA

AF:

0.331

AC:

2713

ExAC

AF:

0.407

AC:

49191

Asia WGS

AF:

0.595

AC:

2071

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Apr 20, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

PIGB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Developmental and epileptic encephalopathy, 80

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.031

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.033

T;T

MetaRNN

Benign

0.0000020

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-3.4

N;.

PrimateAI

Benign

0.35

PROVEAN

Benign

2.6

N;.

REVEL

Benign

0.11

Sift

Benign

0.74

T;.

Sift4G

Benign

0.54

T;T

Polyphen

0.0

B;.

Vest4

0.067

MPC

0.064

ClinPred

0.0085

GERP RS

4.8

Varity_R

0.059

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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