1-89147643-C-A

Variant names:

• chr1-89147643-C-A
• rs186580098
• NM_207398.3:c.1289G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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]

LOC105378842 (HGNC:):

ACMG classification

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
GBP7	NM_207398.3	c.1289G>T	p.Gly430Val	missense_variant	Exon 8 of 11	ENST00000294671.3	NP_997281.2
LOC105378842	XR_001737682.2	n.109-944C>A		intron_variant	Intron 1 of 3
LOC105378842	XR_947579.3	n.232-948C>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBP7	ENST00000294671.3	c.1289G>T	p.Gly430Val	missense_variant	Exon 8 of 11	2	NM_207398.3	ENSP00000294671.2
GBP7	ENST00000650452.1	c.1289G>T	p.Gly430Val	missense_variant	Exon 8 of 9			ENSP00000496924.1
GBP2	ENST00000464839.5	n.-294G>T		non_coding_transcript_exon_variant	Exon 3 of 15	2		ENSP00000434282.1
GBP2	ENST00000464839.5	n.-294G>T		5_prime_UTR_variant	Exon 3 of 15	2		ENSP00000434282.1

Frequencies

GnomAD3 genomes AF: 0.000605 AC: 92 AN: 152162 Hom.: 0 Cov.: 32

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

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

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

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

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

Other links and lift over

dbSNP: rs186580098; hg19: chr1-89613326;