rs1048425

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T349S) has been classified as Likely benign.

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

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]

LOC105378841 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBP1	NM_002053.3	c.1046C>T	p.Thr349Ile	missense_variant	7/11	ENST00000370473.5	NP_002044.2
LOC105378841	XR_947575.3	n.3207+10043G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBP1	ENST00000370473.5	c.1046C>T	p.Thr349Ile	missense_variant	7/11	1	NM_002053.3	ENSP00000359504	P1
GBP1	ENST00000459831.2	n.1872C>T		non_coding_transcript_exon_variant	6/10	3
GBP1	ENST00000495131.2	n.1266C>T		non_coding_transcript_exon_variant	7/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 106

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1048425; hg19: chr1-89522646;