chr1-89117007-G-C

Variant names:

• chr1-89117007-G-C
• rs1803632
• NM_004120.5:c.853C>G

Variant summary

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

The NM_004120.5(GBP2):​c.853C>G​(p.Pro285Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,612,582 control chromosomes in the GnomAD database, including 355,092 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.63 (31153 hom., cov: 31)
  • Exomes 𝑓: 0.66 (323939 hom.)
• Consequence: GBP2 NM_004120.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864
• Publications: 53 publications found

Genes affected

GBP2 (HGNC:4183): (guanylate binding protein 2) This gene belongs to the guanine-binding protein (GBP) family, which includes interferon-induced proteins that can bind to guanine nucleotides (GMP, GDP and GTP). The encoded protein is a GTPase which hydrolyzes GTP, predominantly to GDP. The protein may play a role as a marker of squamous cell carcinomas. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.7105152E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004120.5. 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
	GBP2	NM_004120.5	MANE Select	c.853C>G	p.Pro285Ala	missense	Exon 6 of 11	NP_004111.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP2	ENST00000370466.4	TSL:1 MANE Select	c.853C>G	p.Pro285Ala	missense	Exon 6 of 11	ENSP00000359497.3
	GBP2	ENST00000875570.1		c.853C>G	p.Pro285Ala	missense	Exon 6 of 11	ENSP00000545629.1
	GBP2	ENST00000875572.1		c.853C>G	p.Pro285Ala	missense	Exon 5 of 10	ENSP00000545631.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96426 AN: 151894 Hom.: 31133 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.674 AC: 169258 AN: 251234 AF XY: 0.673

Gnomad AFR exome AF: 0.507

Gnomad AMR exome AF: 0.708

Gnomad ASJ exome AF: 0.598

Gnomad EAS exome AF: 0.778

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.660

Gnomad OTH exome AF: 0.653

GnomAD4 exome AF: 0.664 AC: 970350 AN: 1460568 Hom.: 323939 Cov.: 43 AF XY: 0.665 AC XY: 483058 AN XY: 726616

African (AFR) AF: 0.511 AC: 17073 AN: 33436

American (AMR) AF: 0.701 AC: 31335 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 15684 AN: 26124

East Asian (EAS) AF: 0.778 AC: 30872 AN: 39690

South Asian (SAS) AF: 0.660 AC: 56943 AN: 86236

European-Finnish (FIN) AF: 0.778 AC: 41567 AN: 53416

Middle Eastern (MID) AF: 0.622 AC: 3589 AN: 5766

European-Non Finnish (NFE) AF: 0.661 AC: 734110 AN: 1110842

Other (OTH) AF: 0.649 AC: 39177 AN: 60350

GnomAD4 genome AF: 0.635 AC: 96487 AN: 152014 Hom.: 31153 Cov.: 31 AF XY: 0.641 AC XY: 47628 AN XY: 74294

African (AFR) AF: 0.520 AC: 21533 AN: 41438

American (AMR) AF: 0.645 AC: 9838 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2080 AN: 3466

East Asian (EAS) AF: 0.784 AC: 4056 AN: 5172

South Asian (SAS) AF: 0.664 AC: 3199 AN: 4820

European-Finnish (FIN) AF: 0.798 AC: 8435 AN: 10576

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45318 AN: 67974

Other (OTH) AF: 0.628 AC: 1323 AN: 2106

Alfa AF: 0.644 Hom.: 22260

Bravo AF: 0.618

TwinsUK AF: 0.666 AC: 2470

ALSPAC AF: 0.663 AC: 2555

ESP6500AA AF: 0.519 AC: 2288

ESP6500EA AF: 0.663 AC: 5701

ExAC AF: 0.670 AC: 81337

Asia WGS AF: 0.672 AC: 2337 AN: 3478

EpiCase AF: 0.659

EpiControl AF: 0.634

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.9
DANN	Benign	0.11
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.86
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.016
Sift	Benign	0.84	T
Sift4G	Benign	0.67	T
Polyphen		0.0040	B
Vest4		0.034
MPC		0.092
ClinPred		0.00047	T
GERP RS		-0.66
Varity_R		0.026
gMVP		0.070
Mutation Taster		=96/4	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: rs1803632; hg19: chr1-89582690; COSMIC: COSV65068867; COSMIC: COSV65068867;