NM_004855.5:c.418-168G>A

Variant names:

• chr15-55327363-G-A
• rs7174876
• NM_004855.5:c.418-168G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004855.5(PIGB):​c.418-168G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,546 control chromosomes in the GnomAD database, including 7,235 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 0.28 (7235 hom., cov: 32)
• Consequence: PIGB NM_004855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 80

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGB	NM_004855.5	c.418-168G>A		intron_variant	Intron 3 of 11	ENST00000164305.10	NP_004846.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGB	ENST00000164305.10	c.418-168G>A		intron_variant	Intron 3 of 11	1	NM_004855.5	ENSP00000164305.5
PIGB	ENST00000566999.5	c.391-168G>A		intron_variant	Intron 3 of 5	3		ENSP00000456531.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42524 AN: 151436 Hom.: 7225 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.272

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.281 AC: 42562 AN: 151546 Hom.: 7235 Cov.: 32 AF XY: 0.281 AC XY: 20816 AN XY: 74076

African (AFR) AF: 0.451 AC: 18610 AN: 41304

American (AMR) AF: 0.282 AC: 4289 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3468

East Asian (EAS) AF: 0.552 AC: 2848 AN: 5160

South Asian (SAS) AF: 0.278 AC: 1333 AN: 4802

European-Finnish (FIN) AF: 0.175 AC: 1816 AN: 10390

Middle Eastern (MID) AF: 0.191 AC: 55 AN: 288

European-Non Finnish (NFE) AF: 0.179 AC: 12124 AN: 67902

Other (OTH) AF: 0.270 AC: 567 AN: 2102

Alfa AF: 0.139 Hom.: 326

Bravo AF: 0.299

Asia WGS AF: 0.379 AC: 1317 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.85
DANN	Benign	0.094
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7174876; hg19: chr15-55619561;