chr1-89147771-C-A

Variant names:

• chr1-89147771-C-A
• NM_207398.3:c.1161G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_207398.3(GBP7):​c.1161G>T​(p.Met387Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GBP7 NM_207398.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.465
• Publications: 0 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044493496).
• BP6: Variant 1-89147771-C-A is Benign according to our data. Variant chr1-89147771-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2236826.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1161G>T	p.Met387Ile	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.1161G>T	p.Met387Ile	missense	Exon 8 of 11	ENSP00000294671.2	Q8N8V2
	GBP7	ENST00000897023.1		c.1158G>T	p.Met386Ile	missense	Exon 8 of 11	ENSP00000567082.1
	GBP7	ENST00000897020.1		c.1035G>T	p.Met345Ile	missense	Exon 8 of 11	ENSP00000567079.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.013
DANN	Benign	0.45
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.080	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.8	N
PhyloP100		-0.47
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.026
Sift	Benign	0.51	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.46		Gain of catalytic residue at M387 (P = 0.0258)
MVP		0.014
MPC		0.035
ClinPred		0.61	D
GERP RS		-3.3
Varity_R		0.049
gMVP		0.12
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

hg19: chr1-89613454;