15-55319235-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004855.5(PIGB):c.-16A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,597,260 control chromosomes in the GnomAD database, including 37,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4515 hom., cov: 32)
  • Exomes 𝑓: 0.20 (32746 hom.)
• Consequence: PIGB NM_004855.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.339

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-55319235-A-G is Benign according to our data. Variant chr15-55319235-A-G is described in ClinVar as [Benign]. Clinvar id is 1327019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGB	NM_004855.5	c.-16A>G		5_prime_UTR_variant	1/12	ENST00000164305.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGB	ENST00000164305.10	c.-16A>G		5_prime_UTR_variant	1/12	1	NM_004855.5	P2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34931 AN: 152058 Hom.: 4507 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.235

GnomAD3 exomes AF: 0.242 AC: 53676 AN: 221532 Hom.: 7876 AF XY: 0.237 AC XY: 28443 AN XY: 120214

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.575

Gnomad SAS exome AF: 0.279

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.201 AC: 289767 AN: 1445084 Hom.: 32746 Cov.: 32 AF XY: 0.201 AC XY: 144396 AN XY: 717112

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.230 AC: 34960 AN: 152176 Hom.: 4515 Cov.: 32 AF XY: 0.233 AC XY: 17297 AN XY: 74390

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.233

Alfa AF: 0.193 Hom.: 675

Bravo AF: 0.241

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 80 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.4
Dann	Benign	0.63

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: rs28668016; hg19: chr15-55611433;