rs1048425

Variant names:

• chr1-89056963-G-A
• rs1048425
• NM_002053.3:c.1046C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-89056963-G-A
• chr1-89056963-G-C

Variant summary

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

The NM_002053.3(GBP1):​c.1046C>T​(p.Thr349Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GBP1 NM_002053.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57
• Publications: 30 publications found

Genes affected

GBP1 (HGNC:4182): (guanylate binding protein 1) Guanylate binding protein expression is induced by interferon. Guanylate binding proteins are characterized by their ability to specifically bind guanine nucleotides (GMP, GDP, and GTP) and are distinguished from the GTP-binding proteins by the presence of 2 binding motifs rather than 3. [provided by RefSeq, Jul 2008]

ENSG00000307222 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002053.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP1	NM_002053.3	MANE Select	c.1046C>T	p.Thr349Ile	missense	Exon 7 of 11	NP_002044.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP1	ENST00000370473.5	TSL:1 MANE Select	c.1046C>T	p.Thr349Ile	missense	Exon 7 of 11	ENSP00000359504.4
	GBP1	ENST00000459831.2	TSL:3	n.1872C>T		non_coding_transcript_exon	Exon 6 of 10
	GBP1	ENST00000495131.2	TSL:2	n.1266C>T		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 106

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 14706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0096	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		2.6
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.32
MutPred		0.60		Gain of loop (P = 0.0079)
MVP		0.58
MPC		0.081
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.64
gMVP		0.36
Mutation Taster		=92/8	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: rs1048425; hg19: chr1-89522646;