rs12050587

Variant names:

• chr15-55335330-A-G
• rs12050587
• NM_004855.5:c.794+1323A>G

Variant summary

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

The ENST00000164305.10(PIGB):​c.794+1323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,070 control chromosomes in the GnomAD database, including 8,522 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 0.32 (8522 hom., cov: 32)
• Consequence: PIGB ENST00000164305.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000164305.10. 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
	PIGB	NM_004855.5	MANE Select	c.794+1323A>G		intron	N/A	NP_004846.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGB	ENST00000164305.10	TSL:1 MANE Select	c.794+1323A>G		intron	N/A	ENSP00000164305.5
	PIGB	ENST00000539642.5	TSL:5	c.797+1323A>G		intron	N/A	ENSP00000438963.2
	PIGB	ENST00000565367.5	TSL:2	n.*30+1323A>G		intron	N/A	ENSP00000455943.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48195 AN: 151952 Hom.: 8509 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.317 AC: 48242 AN: 152070 Hom.: 8522 Cov.: 32 AF XY: 0.318 AC XY: 23657 AN XY: 74360

African (AFR) AF: 0.445 AC: 18453 AN: 41466

American (AMR) AF: 0.336 AC: 5127 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1046 AN: 3468

East Asian (EAS) AF: 0.561 AC: 2894 AN: 5162

South Asian (SAS) AF: 0.331 AC: 1597 AN: 4824

European-Finnish (FIN) AF: 0.224 AC: 2368 AN: 10584

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15811 AN: 67988

Other (OTH) AF: 0.310 AC: 653 AN: 2106

Alfa AF: 0.253 Hom.: 2623

Bravo AF: 0.332

Asia WGS AF: 0.426 AC: 1484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.64
PhyloP100		-1.2
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: rs12050587; hg19: chr15-55627528;