1-89147643-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_207398.3(GBP7):​c.1289G>T​(p.Gly430Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000832 in 1,614,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G430A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00086 ( 1 hom. )

Consequence

GBP7
NM_207398.3 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82
Variant links:
Genes affected
GBP7 (HGNC:29606): (guanylate binding protein 7) Guanylate-binding proteins, such as GBP7, are induced by interferon and hydrolyze GTP to both GDP and GMP (Olszewski et al., 2006 [PubMed 16689661]).[supplied by OMIM, Dec 2008]
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30119368).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GBP7NM_207398.3 linkc.1289G>T p.Gly430Val missense_variant Exon 8 of 11 ENST00000294671.3 NP_997281.2 Q8N8V2
LOC105378842XR_001737682.2 linkn.109-944C>A intron_variant Intron 1 of 3
LOC105378842XR_947579.3 linkn.232-948C>A intron_variant Intron 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GBP7ENST00000294671.3 linkc.1289G>T p.Gly430Val missense_variant Exon 8 of 11 2 NM_207398.3 ENSP00000294671.2 Q8N8V2
GBP7ENST00000650452.1 linkc.1289G>T p.Gly430Val missense_variant Exon 8 of 9 ENSP00000496924.1 A0A3B3IRS3
GBP2ENST00000464839.5 linkn.-294G>T non_coding_transcript_exon_variant Exon 3 of 15 2 ENSP00000434282.1 P32456
GBP2ENST00000464839.5 linkn.-294G>T 5_prime_UTR_variant Exon 3 of 15 2 ENSP00000434282.1 P32456

Frequencies

GnomAD3 genomes
AF:
0.000605
AC:
92
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.000754
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000897
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000549
AC:
138
AN:
251422
Hom.:
1
AF XY:
0.000692
AC XY:
94
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.000693
Gnomad NFE exome
AF:
0.000879
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000856
AC:
1251
AN:
1461854
Hom.:
1
Cov.:
31
AF XY:
0.000851
AC XY:
619
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000243
Gnomad4 FIN exome
AF:
0.000730
Gnomad4 NFE exome
AF:
0.00102
Gnomad4 OTH exome
AF:
0.000613
GnomAD4 genome
AF:
0.000604
AC:
92
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.000698
AC XY:
52
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.000754
Gnomad4 NFE
AF:
0.000897
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000598
Hom.:
0
Bravo
AF:
0.000472
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000486
AC:
59
EpiCase
AF:
0.000873
EpiControl
AF:
0.00107

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1289G>T (p.G430V) alteration is located in exon 8 (coding exon 7) of the GBP7 gene. This alteration results from a G to T substitution at nucleotide position 1289, causing the glycine (G) at amino acid position 430 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Uncertain
0.0
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.
Eigen
Uncertain
0.42
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Uncertain
0.56
D
MutationAssessor
Pathogenic
4.1
H;.
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-8.4
D;.
REVEL
Uncertain
0.57
Sift
Uncertain
0.0010
D;.
Sift4G
Pathogenic
0.0010
D;.
Polyphen
1.0
D;.
Vest4
0.50
MVP
0.81
MPC
0.27
ClinPred
0.33
T
GERP RS
3.0
Varity_R
0.93
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs186580098; hg19: chr1-89613326; API