chr1-89056855-G-T

Variant names:

• chr1-89056855-G-T
• rs147875713
• NM_002053.3:c.1154C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002053.3(GBP1):​c.1154C>A​(p.Ala385Glu) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. A385V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GBP1 NM_002053.3 missense, splice_region
• Scores: Splicing: ADA: 0.00007549
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.32

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040431112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP1	NM_002053.3	c.1154C>A	p.Ala385Glu	missense_variant, splice_region_variant	Exon 7 of 11	ENST00000370473.5	NP_002044.2
LOC105378841	XR_947575.3	n.3207+9935G>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBP1	ENST00000370473.5	c.1154C>A	p.Ala385Glu	missense_variant, splice_region_variant	Exon 7 of 11	1	NM_002053.3	ENSP00000359504.4
GBP1	ENST00000459831.2	n.1980C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 6 of 10	3
GBP1	ENST00000495131.2	n.1374C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 7 of 10	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0080
DANN	Benign	0.19
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.059	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.017
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.17
MutPred		0.48		Gain of ubiquitination at K382 (P = 0.0482);
MVP		0.18
MPC		0.39
ClinPred		0.032	T
GERP RS		-9.6
Varity_R		0.18
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000075
dbscSNV1_RF	Benign	0.080
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: rs147875713; hg19: chr1-89522538;