Genetic Variant GBP2:c.1660-52C>T (chr1-89108343-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004120.5(GBP2):c.1660-52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,136,592 control chromosomes in the GnomAD database, including 286,483 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 41701 hom., cov: 32)

Exomes 𝑓: 0.70 ( 244782 hom. )

Consequence

GBP2
NM_004120.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.198

Publications

17 publications found

Variant links:

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]

GBP2 links:

ENSG00000307222 (HGNC:):

ENSG00000307222 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 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.1660-52C>T		intron	N/A	NP_004111.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GBP2	ENST00000370466.4	TSL:1 MANE Select	c.1660-52C>T	intron	N/A	ENSP00000359497.3	P32456
GBP2	ENST00000875570.1		c.1672-52C>T	intron	N/A	ENSP00000545629.1
GBP2	ENST00000875572.1		c.1660-52C>T	intron	N/A	ENSP00000545631.1

Frequencies

GnomAD3 genomes

AF:

0.738

AC:

112161

AN:

152070

Hom.:

41653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.699

Gnomad FIN

AF:

0.812

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.693

Gnomad OTH

AF:

0.715

GnomAD2 exomes

AF:

0.721

AC:

159690

AN:

221496

AF XY:

0.714

show subpopulations

Gnomad AFR exome

AF:

0.815

Gnomad AMR exome

AF:

0.750

Gnomad ASJ exome

AF:

0.630

Gnomad EAS exome

AF:

0.793

Gnomad FIN exome

AF:

0.803

Gnomad NFE exome

AF:

0.687

Gnomad OTH exome

AF:

0.693

GnomAD4 exome

AF:

0.704

AC:

692868

AN:

984404

Hom.:

244782

Cov.:

AF XY:

0.703

AC XY:

358240

AN XY:

509648

show subpopulations

African (AFR)

AF:

0.820

AC:

19029

AN:

23210

American (AMR)

AF:

0.744

AC:

27441

AN:

36882

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

13678

AN:

21528

East Asian (EAS)

AF:

0.781

AC:

28563

AN:

36576

South Asian (SAS)

AF:

0.696

AC:

49992

AN:

71870

European-Finnish (FIN)

AF:

0.795

AC:

40473

AN:

50904

Middle Eastern (MID)

AF:

0.713

AC:

3342

AN:

4688

European-Non Finnish (NFE)

AF:

0.690

AC:

479320

AN:

694440

Other (OTH)

AF:

0.700

AC:

31030

AN:

44306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

9766

19533

29299

39066

48832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9752

19504

29256

39008

48760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.738

AC:

112265

AN:

152188

Hom.:

41701

Cov.:

AF XY:

0.740

AC XY:

55047

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.815

AC:

33819

AN:

41516

American (AMR)

AF:

0.703

AC:

10751

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

2202

AN:

3470

East Asian (EAS)

AF:

0.794

AC:

4108

AN:

5174

South Asian (SAS)

AF:

0.699

AC:

3373

AN:

4826

European-Finnish (FIN)

AF:

0.812

AC:

8593

AN:

10578

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.693

AC:

47149

AN:

68002

Other (OTH)

AF:

0.717

AC:

1518

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1509

3017

4526

6034

7543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

850

1700

2550

3400

4250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.689

Hom.:

23404

Bravo

AF:

0.732

Asia WGS

AF:

0.755

AC:

2626

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

(source)

DANN

Benign

0.60

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over