1-89117007-G-T

Variant names:

• chr1-89117007-G-T
• rs1803632
• NM_004120.5:c.853C>A

Variant summary

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

The NM_004120.5(GBP2):​c.853C>A​(p.Pro285Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GBP2 NM_004120.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864
• Publications: 53 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]

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=0.06552246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP2	NM_004120.5	c.853C>A	p.Pro285Thr	missense_variant	Exon 6 of 11	ENST00000370466.4	NP_004111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBP2	ENST00000370466.4	c.853C>A	p.Pro285Thr	missense_variant	Exon 6 of 11	1	NM_004120.5	ENSP00000359497.3
GBP2	ENST00000463660.1	n.2872C>A		non_coding_transcript_exon_variant	Exon 2 of 5	2
GBP2	ENST00000464839.5	n.853C>A		non_coding_transcript_exon_variant	Exon 9 of 15	2		ENSP00000434282.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 22260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.8
DANN	Benign	0.18
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00087	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.1	N
PhyloP100		-0.86
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.043
Sift	Benign	0.70	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.031
MutPred		0.28		Loss of loop (P = 0.1242);
MVP		0.12
MPC		0.11
ClinPred		0.034	T
GERP RS		-0.66
Varity_R		0.043
gMVP		0.099
Mutation Taster		=94/6	polymorphism

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: rs1803632; hg19: chr1-89582690;