Variant 1-89007770-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018284.3(GBP3):c.1742T>C(p.Leu581Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,608,236 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0091 ( 13 hom., cov: 32)

Exomes 𝑓: 0.013 ( 161 hom. )

Consequence

GBP3
NM_018284.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21

Variant links:

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]

GBP3 links:

GBP3 (HGNC:):

GBP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005427271).

BP6

Variant 1-89007770-A-G is Benign according to our data. Variant chr1-89007770-A-G is described in ClinVar as [Benign]. Clinvar id is 2638916.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.013 (18996/1456910) while in subpopulation NFE AF= 0.0155 (17214/1109480). AF 95% confidence interval is 0.0153. There are 161 homozygotes in gnomad4_exome. There are 9121 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBP3	NM_018284.3 linkuse as main transcript	c.1742T>C	p.Leu581Pro	missense_variant	11/11	ENST00000370481.9	NP_060754.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBP3	ENST00000370481.9 linkuse as main transcript	c.1742T>C	p.Leu581Pro	missense_variant	11/11	1	NM_018284.3	ENSP00000359512.4		Q9H0R5-1

Frequencies

GnomAD3 genomes

AF:

0.00911

AC:

1377

AN:

151212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.00505

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0145

Gnomad OTH

AF:

0.0111

GnomAD3 exomes

AF:

0.00833

AC:

2070

AN:

248352

Hom.:

AF XY:

0.00830

AC XY:

1114

AN XY:

134246

show subpopulations

Gnomad AFR exome

AF:

0.00285

Gnomad AMR exome

AF:

0.00498

Gnomad ASJ exome

AF:

0.0163

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00130

Gnomad FIN exome

AF:

0.00543

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.00893

GnomAD4 exome

AF:

0.0130

AC:

18996

AN:

1456910

Hom.:

161

Cov.:

AF XY:

0.0126

AC XY:

9121

AN XY:

724832

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00596

Gnomad4 ASJ exome

AF:

0.0137

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.00543

Gnomad4 NFE exome

AF:

0.0155

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.00910

AC:

1377

AN:

151326

Hom.:

Cov.:

AF XY:

0.00832

AC XY:

615

AN XY:

73912

show subpopulations

Gnomad4 AFR

AF:

0.00257

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.00505

Gnomad4 NFE

AF:

0.0145

Gnomad4 OTH

AF:

0.0110

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.0101

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0179

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.00791

AC:

960

EpiCase

AF:

0.0133

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

GBP3: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.030

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.86

REVEL

Benign

0.051

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.047

Polyphen

0.40

Vest4

0.33

MVP

0.16

MPC

0.12

ClinPred

0.025

GERP RS

-0.15

Varity_R

0.49

gMVP

0.14

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over