rs8043415

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

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

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGB	NM_004855.5	MANE Select	c.1527C>T	p.Ser509Ser	synonymous	Exon 12 of 12	NP_004846.4
	CCPG1	NM_001204450.2	MANE Select	c.*926G>A		3_prime_UTR	Exon 9 of 9	NP_001191379.1	Q9ULG6-5
	CCPG1	NM_004748.6		c.*4205G>A		3_prime_UTR	Exon 8 of 8	NP_004739.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGB	ENST00000164305.10	TSL:1 MANE Select	c.1527C>T	p.Ser509Ser	synonymous	Exon 12 of 12	ENSP00000164305.5	Q92521
	CCPG1	ENST00000442196.8	TSL:2 MANE Select	c.*926G>A		3_prime_UTR	Exon 9 of 9	ENSP00000403400.3	Q9ULG6-5
	CCPG1	ENST00000310958.10	TSL:1	c.*4205G>A		3_prime_UTR	Exon 8 of 8	ENSP00000311656.6	Q9ULG6-1

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

GnomAD2 exomes AF: 0.0758 AC: 18560 AN: 244836 AF XY: 0.0778

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 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

African (AFR) AF: 0.212 AC: 6971 AN: 32936

American (AMR) AF: 0.0485 AC: 2119 AN: 43660

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2954 AN: 25866

East Asian (EAS) AF: 0.000253 AC: 10 AN: 39580

South Asian (SAS) AF: 0.112 AC: 9473 AN: 84948

European-Finnish (FIN) AF: 0.0557 AC: 2970 AN: 53344

Middle Eastern (MID) AF: 0.0985 AC: 565 AN: 5734

European-Non Finnish (NFE) AF: 0.0707 AC: 78076 AN: 1103656

Other (OTH) AF: 0.0806 AC: 4831 AN: 59938

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

African (AFR) AF: 0.206 AC: 8566 AN: 41490

American (AMR) AF: 0.0776 AC: 1186 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5184

South Asian (SAS) AF: 0.101 AC: 485 AN: 4824

European-Finnish (FIN) AF: 0.0572 AC: 606 AN: 10596

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0709 AC: 4820 AN: 68010

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.0910 Hom.: 503

Bravo AF: 0.110

Asia WGS AF: 0.0470 AC: 163 AN: 3476

EpiCase AF: 0.0760

EpiControl AF: 0.0758

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	PIGB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.3
DANN	Benign	0.84
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8043415; hg19: chr15-55647492;