1-89056963-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002053.3(GBP1):​c.1046C>G​(p.Thr349Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,614,032 control chromosomes in the GnomAD database, including 483,355 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.77 (45183 hom., cov: 32)
  • Exomes 𝑓: 0.77 (438172 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.0006142E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

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>G	p.Thr349Ser	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>G	p.Thr349Ser	missense	Exon 7 of 11	ENSP00000359504.4
	GBP1	ENST00000459831.2	TSL:3	n.1872C>G		non_coding_transcript_exon	Exon 6 of 10
	GBP1	ENST00000495131.2	TSL:2	n.1266C>G		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116807 AN: 152030 Hom.: 45139 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.765

GnomAD2 exomes AF: 0.739 AC: 185791 AN: 251470 AF XY: 0.748

Gnomad AFR exome AF: 0.809

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.775

Gnomad EAS exome AF: 0.582

Gnomad FIN exome AF: 0.760

Gnomad NFE exome AF: 0.784

Gnomad OTH exome AF: 0.752

GnomAD4 exome AF: 0.772 AC: 1128457 AN: 1461882 Hom.: 438172 Cov.: 106 AF XY: 0.773 AC XY: 562249 AN XY: 727244

African (AFR) AF: 0.808 AC: 27066 AN: 33480

American (AMR) AF: 0.586 AC: 26221 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 20166 AN: 26136

East Asian (EAS) AF: 0.535 AC: 21250 AN: 39700

South Asian (SAS) AF: 0.777 AC: 66995 AN: 86258

European-Finnish (FIN) AF: 0.756 AC: 40359 AN: 53420

Middle Eastern (MID) AF: 0.710 AC: 4096 AN: 5768

European-Non Finnish (NFE) AF: 0.788 AC: 875825 AN: 1112000

Other (OTH) AF: 0.770 AC: 46479 AN: 60396

GnomAD4 genome AF: 0.768 AC: 116905 AN: 152150 Hom.: 45183 Cov.: 32 AF XY: 0.765 AC XY: 56891 AN XY: 74370

African (AFR) AF: 0.805 AC: 33417 AN: 41510

American (AMR) AF: 0.653 AC: 9980 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2643 AN: 3470

East Asian (EAS) AF: 0.561 AC: 2894 AN: 5160

South Asian (SAS) AF: 0.780 AC: 3769 AN: 4830

European-Finnish (FIN) AF: 0.759 AC: 8017 AN: 10568

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.788 AC: 53566 AN: 68012

Other (OTH) AF: 0.768 AC: 1622 AN: 2112

Alfa AF: 0.780 Hom.: 14706

Bravo AF: 0.760

TwinsUK AF: 0.789 AC: 2927

ALSPAC AF: 0.786 AC: 3028

ESP6500AA AF: 0.813 AC: 3581

ESP6500EA AF: 0.784 AC: 6746

ExAC AF: 0.745 AC: 90441

Asia WGS AF: 0.708 AC: 2461 AN: 3478

EpiCase AF: 0.783

EpiControl AF: 0.792

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0000050	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.6
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.13
Sift	Benign	0.091	T
Sift4G	Benign	0.093	T
Polyphen		0.25	B
Vest4		0.052
MutPred		0.51		Gain of disorder (P = 0.0459)
MPC		0.068
ClinPred		0.072	T
GERP RS		3.9
Varity_R		0.55
gMVP		0.12
Mutation Taster		=99/1	polymorphism (auto)

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; COSMIC: COSV65082611; COSMIC: COSV65082611;