chr15-55330497-T-C

Variant names:

• chr15-55330497-T-C
• rs7183960
• NM_004855.5:c.653+643T>C

Variant summary

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

The NM_004855.5(PIGB):​c.653+643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,956 control chromosomes in the GnomAD database, including 8,732 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 (8732 hom., cov: 32)
• Consequence: PIGB NM_004855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 9 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=-0.97).
• 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: NM_004855.5. 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.653+643T>C		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.653+643T>C		intron	N/A	ENSP00000164305.5
	PIGB	ENST00000566999.5	TSL:3	c.626+643T>C		intron	N/A	ENSP00000456531.1
	PIGB	ENST00000539642.5	TSL:5	c.656+643T>C		intron	N/A	ENSP00000438963.2

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48930 AN: 151838 Hom.: 8719 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.322 AC: 48981 AN: 151956 Hom.: 8732 Cov.: 32 AF XY: 0.325 AC XY: 24148 AN XY: 74274

African (AFR) AF: 0.449 AC: 18604 AN: 41400

American (AMR) AF: 0.335 AC: 5120 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3472

East Asian (EAS) AF: 0.561 AC: 2896 AN: 5164

South Asian (SAS) AF: 0.326 AC: 1570 AN: 4822

European-Finnish (FIN) AF: 0.273 AC: 2878 AN: 10552

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15849 AN: 67974

Other (OTH) AF: 0.313 AC: 660 AN: 2110

Alfa AF: 0.263 Hom.: 15574

Bravo AF: 0.333

Asia WGS AF: 0.425 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.12
DANN	Benign	0.32
PhyloP100		-1.5
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: rs7183960; hg19: chr15-55622695;