rs1488928061

Variant names:

• chr15-55355411-C-G
• rs1488928061
• NM_004855.5:c.1644C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-55355411-C-G
• chr15-55355411-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004855.5(PIGB):​c.1644C>G​(p.Phe548Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F548F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIGB NM_004855.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032452255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGB	NM_004855.5	c.1644C>G	p.Phe548Leu	missense_variant	Exon 12 of 12	ENST00000164305.10	NP_004846.4
CCPG1	NM_001204450.2	c.*809G>C		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.1644C>G	p.Phe548Leu	missense_variant	Exon 12 of 12	1	NM_004855.5	ENSP00000164305.5
CCPG1	ENST00000442196.8	c.*809G>C		3_prime_UTR_variant	Exon 9 of 9	2	NM_001204450.2	ENSP00000403400.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.73
DEOGEN2	Benign	0.0013	T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.1	N;.
PhyloP100		0.33
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.070	N;.
REVEL	Benign	0.14
Sift	Benign	0.83	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.016
MutPred		0.26		Loss of methylation at K547 (P = 0.0332);.;
MVP		0.35
MPC		0.047
ClinPred		0.086	T
GERP RS		4.7
Varity_R		0.054
gMVP		0.15

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: rs1488928061; hg19: chr15-55647609;