Genetic Variant NM_004120.5:c.429-613A>G (chr1-89118386-T-C) – 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.429-613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,114 control chromosomes in the GnomAD database, including 13,528 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 0.40 ( 13525 hom., cov: 32)

Exomes 𝑓: 0.41 ( 3 hom. )

Consequence

GBP2
NM_004120.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.322

Publications

11 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:

LOC112268267 (HGNC:):

LOC112268267 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP2	NM_004120.5 link	c.429-613A>G		intron_variant	Intron 4 of 10	ENST00000370466.4	NP_004111.2	P32456Q8TCE5
LOC112268267	XR_007066213.1 link	n.265+344T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GBP2	ENST00000370466.4 link	c.429-613A>G	intron_variant	Intron 4 of 10	1	NM_004120.5	ENSP00000359497.3	P32456
GBP2	ENST00000463660.1 link	n.1835A>G	non_coding_transcript_exon_variant	Exon 1 of 5	2
GBP2	ENST00000464839.5 link	n.429-613A>G	intron_variant	Intron 7 of 14	2		ENSP00000434282.1	P32456

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60518

AN:

151962

Hom.:

13528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.405

GnomAD4 exome

AF:

0.412

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.462

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.398

AC:

60511

AN:

152080

Hom.:

13525

Cov.:

AF XY:

0.402

AC XY:

29913

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.202

AC:

8385

AN:

41506

American (AMR)

AF:

0.320

AC:

4887

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

1427

AN:

3466

East Asian (EAS)

AF:

0.399

AC:

2063

AN:

5168

South Asian (SAS)

AF:

0.487

AC:

2349

AN:

4824

European-Finnish (FIN)

AF:

0.584

AC:

6167

AN:

10566

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.498

AC:

33836

AN:

67964

Other (OTH)

AF:

0.403

AC:

849

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1719

3438

5158

6877

8596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.453

Hom.:

27467

Bravo

AF:

0.366

Asia WGS

AF:

0.408

AC:

1420

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.5

(source)

DANN

Benign

0.76

PhyloP100

0.32

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over