15-55340661-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.04

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]

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]

ACMG classification

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	UniProt
PIGB	NM_004855.5	c.896G>T	p.Trp299Leu	missense_variant	8/12	ENST00000164305.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGB	ENST00000164305.10	c.896G>T	p.Trp299Leu	missense_variant	8/12	1	NM_004855.5	P2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73362 AN: 151560 Hom.: 21084 Cov.: 30

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

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.: 34 AF XY: 0.360 AC XY: 260936 AN XY: 725560

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.: 30 AF XY: 0.481 AC XY: 35648 AN XY: 74086

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2020	- -

PIGB-related disorder Benign:1

Benign, criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	11
Dann	Benign	0.93
DEOGEN2	Benign	0.0018	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.033	T;T
MetaRNN	Benign	0.0000020	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-3.4	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.35	T
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	T
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

Other links and lift over

dbSNP: rs678892; hg19: chr15-55632859; COSMIC: COSV51241821; COSMIC: COSV51241821;