rs200077424

Variant names:

• chr1-89108281-C-A
• rs200077424
• NM_004120.5:c.1670G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-89108281-C-A
• chr1-89108281-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004120.5(GBP2):​c.1670G>T​(p.Arg557Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R557C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GBP2 NM_004120.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.62

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13455328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP2	NM_004120.5	c.1670G>T	p.Arg557Leu	missense_variant	Exon 11 of 11	ENST00000370466.4	NP_004111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBP2	ENST00000370466.4	c.1670G>T	p.Arg557Leu	missense_variant	Exon 11 of 11	1	NM_004120.5	ENSP00000359497.3
GBP2	ENST00000464839.5	n.1670G>T		non_coding_transcript_exon_variant	Exon 14 of 15	2		ENSP00000434282.1
GBP2	ENST00000493802.5	n.630G>T		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000229 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.59
DANN	Benign	0.88
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.032	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.053
Sift	Benign	0.12	T
Sift4G	Benign	0.29	T
Polyphen		0.0070	B
Vest4		0.15
MutPred		0.55		Gain of ubiquitination at K560 (P = 0.0972);
MVP		0.17
MPC		0.12
ClinPred		0.10	T
GERP RS		-6.8
Varity_R		0.085
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200077424; hg19: chr1-89573964;