chr1-89053377-C-T

Variant names:

• chr1-89053377-C-T
• rs150379396
• NM_002053.3:c.1757G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002053.3(GBP1):​c.1757G>A​(p.Arg586Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,613,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: GBP1 NM_002053.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.498
• Publications: 6 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04762408).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP1	NM_002053.3	MANE Select	c.1757G>A	p.Arg586Gln	missense	Exon 11 of 11	NP_002044.2	P32455

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP1	ENST00000370473.5	TSL:1 MANE Select	c.1757G>A	p.Arg586Gln	missense	Exon 11 of 11	ENSP00000359504.4	P32455
	GBP1	ENST00000872735.1		c.1757G>A	p.Arg586Gln	missense	Exon 11 of 11	ENSP00000542794.1
	GBP1	ENST00000872736.1		c.1757G>A	p.Arg586Gln	missense	Exon 11 of 11	ENSP00000542795.1

Frequencies

GnomAD3 genomes AF: 0.0000987 AC: 15 AN: 152038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000955 AC: 24 AN: 251304 AF XY: 0.0000957

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000145 AC: 212 AN: 1461228 Hom.: 0 Cov.: 30 AF XY: 0.000138 AC XY: 100 AN XY: 726940

African (AFR) AF: 0.0000299 AC: 1 AN: 33456

American (AMR) AF: 0.0000895 AC: 4 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39684

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000185 AC: 1 AN: 5394

European-Non Finnish (NFE) AF: 0.000166 AC: 185 AN: 1111886

Other (OTH) AF: 0.000232 AC: 14 AN: 60352

GnomAD4 genome AF: 0.0000987 AC: 15 AN: 152038 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74268

African (AFR) AF: 0.0000242 AC: 1 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68002

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000162 Hom.: 0

Bravo AF: 0.0000945

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.6
DANN	Benign	0.38
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.50
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.039
Sift	Benign	0.63	T
Sift4G	Benign	0.61	T
Polyphen		0.0050	B
Vest4		0.082
MVP		0.60
MPC		0.085
ClinPred		0.015	T
GERP RS		2.0
Varity_R		0.038
gMVP		0.077
Mutation Taster		=100/0	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: rs150379396; hg19: chr1-89519060; COSMIC: COSV65083429; COSMIC: COSV65083429;