1-89112582-C-G

Variant names:

• chr1-89112582-C-G
• rs1013130657
• NM_004120.5:c.1252G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004120.5(GBP2):​c.1252G>C​(p.Glu418Gln) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GBP2 NM_004120.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.123
• Publications: 0 publications found

Genes affected

GBP2 (HGNC:4183): (guanylate binding protein 2) This gene belongs to the guanine-binding protein (GBP) family, which includes interferon-induced proteins that can bind to guanine nucleotides (GMP, GDP and GTP). The encoded protein is a GTPase which hydrolyzes GTP, predominantly to GDP. The protein may play a role as a marker of squamous cell carcinomas. [provided by RefSeq, Jul 2013]

ENSG00000307222 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13684627).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004120.5. 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
	GBP2	NM_004120.5	MANE Select	c.1252G>C	p.Glu418Gln	missense	Exon 8 of 11	NP_004111.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP2	ENST00000370466.4	TSL:1 MANE Select	c.1252G>C	p.Glu418Gln	missense	Exon 8 of 11	ENSP00000359497.3	P32456
	GBP2	ENST00000875570.1		c.1252G>C	p.Glu418Gln	missense	Exon 8 of 11	ENSP00000545629.1
	GBP2	ENST00000875572.1		c.1252G>C	p.Glu418Gln	missense	Exon 7 of 10	ENSP00000545631.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.12
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.030
Sift	Benign	0.14	T
Sift4G	Benign	0.26	T
Polyphen		0.75	P
Vest4		0.23
MutPred		0.50		Gain of methylation at K421 (P = 0.0786)
MVP		0.21
MPC		0.24
ClinPred		0.43	T
GERP RS		0.40
Varity_R		0.18
gMVP		0.066
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1013130657; hg19: chr1-89578265;