chr15-55355294-C-T

Variant names:

• chr15-55355294-C-T
• rs8043415
• NM_004855.5:c.1527C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004855.5(PIGB):​c.1527C>T​(p.Ser509Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 1,601,842 control chromosomes in the GnomAD database, including 5,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1244 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4748 hom.)
• Consequence: PIGB NM_004855.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.519

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]

CCPG1 (HGNC:24227): (cell cycle progression 1) Involved in positive regulation of cell cycle and positive regulation of cell population proliferation. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 15-55355294-C-T is Benign according to our data. Variant chr15-55355294-C-T is described in ClinVar as [Benign]. Clinvar id is 1577109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.519 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGB	NM_004855.5	c.1527C>T	p.Ser509Ser	synonymous_variant	Exon 12 of 12	ENST00000164305.10	NP_004846.4
CCPG1	NM_001204450.2	c.*926G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000442196.8	NP_001191379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGB	ENST00000164305.10	c.1527C>T	p.Ser509Ser	synonymous_variant	Exon 12 of 12	1	NM_004855.5	ENSP00000164305.5
CCPG1	ENST00000442196	c.*926G>A		3_prime_UTR_variant	Exon 9 of 9	2	NM_001204450.2	ENSP00000403400.3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16291 AN: 152062 Hom.: 1241 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0758 AC: 18560 AN: 244836 Hom.: 967 AF XY: 0.0778 AC XY: 10342 AN XY: 132868

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.0441

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.000337

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.0520

Gnomad NFE exome AF: 0.0716

Gnomad OTH exome AF: 0.0742

GnomAD4 exome AF: 0.0745 AC: 107969 AN: 1449662 Hom.: 4748 Cov.: 29 AF XY: 0.0756 AC XY: 54555 AN XY: 721440

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.0485

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.000253

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0557

Gnomad4 NFE exome AF: 0.0707

Gnomad4 OTH exome AF: 0.0806

GnomAD4 genome AF: 0.107 AC: 16309 AN: 152180 Hom.: 1244 Cov.: 32 AF XY: 0.105 AC XY: 7809 AN XY: 74398

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0776

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0572

Gnomad4 NFE AF: 0.0709

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.0894 Hom.: 469

Bravo AF: 0.110

Asia WGS AF: 0.0470 AC: 163 AN: 3476

EpiCase AF: 0.0760

EpiControl AF: 0.0758

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

PIGB-related disorder Benign:1

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.3
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs8043415; hg19: chr15-55647492;