rs1290205498

Variant names:

• chr1-89009134-C-G
• rs1290205498
• NM_018284.3:c.1472G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-89009134-C-G
• chr1-89009134-C-T

Variant summary

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

The NM_018284.3(GBP3):​c.1472G>C​(p.Cys491Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,482 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C491Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GBP3 NM_018284.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 0 publications found

Genes affected

GBP3 (HGNC:4184): (guanylate binding protein 3) This gene encodes a member of the guanylate-binding protein (GBP) family. GBPs specifically bind guanine nucleotides (GMP, GDP, and GTP) and contain two of the three consensus motifs found in typical GTP-binding proteins. The encoded protein interacts with a member of the germinal center kinase family. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2017]

ENSG00000307222 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040082753).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018284.3. 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
	GBP3	NM_018284.3	MANE Select	c.1472G>C	p.Cys491Ser	missense	Exon 10 of 11	NP_060754.2	Q9H0R5-1
	GBP3	NM_001436844.1		c.1391G>C	p.Cys464Ser	missense	Exon 10 of 11	NP_001423773.1	A0ABB0MVI2
	GBP3	NM_001319181.2		c.1391G>C	p.Cys464Ser	missense	Exon 10 of 10	NP_001306110.1	Q9H0R5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBP3	ENST00000370481.9	TSL:1 MANE Select	c.1472G>C	p.Cys491Ser	missense	Exon 10 of 11	ENSP00000359512.4	Q9H0R5-1
	GBP3	ENST00000489444.6	TSL:1	n.*105G>C		non_coding_transcript_exon	Exon 8 of 9	ENSP00000437168.2	F6X827
	GBP3	ENST00000493594.6	TSL:1	n.*1282G>C		non_coding_transcript_exon	Exon 11 of 12	ENSP00000456449.1	H3BRX6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250778 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461482 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727028

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111788

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.37
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.11
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.076
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.081
MutPred		0.28		Gain of phosphorylation at C491 (P = 0.0143)
MVP		0.12
MPC		0.050
ClinPred		0.056	T
GERP RS		0.55
Varity_R		0.11
gMVP		0.057
Mutation Taster		=99/1	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

dbSNP: rs1290205498; hg19: chr1-89474817;