rs7174876

Positions:

• chr15-55327363-G-A
• chr15-55327363-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PIGB	NM_004855.5	c.418-168G>A		intron_variant		ENST00000164305.10	NP_004846.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGB	ENST00000164305.10	c.418-168G>A		intron_variant		1	NM_004855.5	ENSP00000164305.5
PIGB	ENST00000566999.5	c.391-168G>A		intron_variant		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

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.270

Alfa AF: 0.127 Hom.: 266

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

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: rs7174876; hg19: chr15-55619561;