chr1-89147643-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. 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. G430E) 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
• Publications: 4 publications found

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]

ENSG00000286802 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30119368).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207398.3. 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
	GBP7	NM_207398.3	MANE Select	c.1289G>T	p.Gly430Val	missense	Exon 8 of 11	NP_997281.2	Q8N8V2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP7	ENST00000294671.3	TSL:2 MANE Select	c.1289G>T	p.Gly430Val	missense	Exon 8 of 11	ENSP00000294671.2	Q8N8V2
	GBP7	ENST00000897023.1		c.1286G>T	p.Gly429Val	missense	Exon 8 of 11	ENSP00000567082.1
	GBP7	ENST00000897020.1		c.1163G>T	p.Gly388Val	missense	Exon 8 of 11	ENSP00000567079.1

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

GnomAD2 exomes AF: 0.000549 AC: 138 AN: 251422 AF XY: 0.000692

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 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

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000268 AC: 12 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86256

European-Finnish (FIN) AF: 0.000730 AC: 39 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00102 AC: 1135 AN: 1111986

Other (OTH) AF: 0.000613 AC: 37 AN: 60396

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.000698 AC XY: 52 AN XY: 74464

African (AFR) AF: 0.000217 AC: 9 AN: 41558

American (AMR) AF: 0.000588 AC: 9 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68022

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000722 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.56	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		1.8
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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs186580098; hg19: chr1-89613326;