Variant 1-89056963-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002053.3(GBP1):c.1046C>G(p.Thr349Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,614,032 control chromosomes in the GnomAD database, including 483,355 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.77 ( 45183 hom., cov: 32)

Exomes 𝑓: 0.77 ( 438172 hom. )

Consequence

GBP1
NM_002053.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.57

Variant links:

Genes affected

GBP1 (HGNC:4182): (guanylate binding protein 1) Guanylate binding protein expression is induced by interferon. Guanylate binding proteins are characterized by their ability to specifically bind guanine nucleotides (GMP, GDP, and GTP) and are distinguished from the GTP-binding proteins by the presence of 2 binding motifs rather than 3. [provided by RefSeq, Jul 2008]

GBP1 links:

LOC105378841 (HGNC:):

LOC105378841 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.0006142E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBP1	NM_002053.3 linkuse as main transcript	c.1046C>G	p.Thr349Ser	missense_variant	7/11	ENST00000370473.5	NP_002044.2
LOC105378841	XR_947575.3 linkuse as main transcript	n.3207+10043G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GBP1	ENST00000370473.5 linkuse as main transcript	c.1046C>G	p.Thr349Ser	missense_variant	7/11	1	NM_002053.3	ENSP00000359504	P1
GBP1	ENST00000459831.2 linkuse as main transcript	n.1872C>G		non_coding_transcript_exon_variant	6/10	3
GBP1	ENST00000495131.2 linkuse as main transcript	n.1266C>G		non_coding_transcript_exon_variant	7/10	2

Frequencies

GnomAD3 genomes

AF:

0.768

AC:

116807

AN:

152030

Hom.:

45139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.856

Gnomad AMR

AF:

0.654

Gnomad ASJ

AF:

0.762

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.780

Gnomad FIN

AF:

0.759

Gnomad MID

AF:

0.739

Gnomad NFE

AF:

0.788

Gnomad OTH

AF:

0.765

GnomAD3 exomes

AF:

0.739

AC:

185791

AN:

251470

Hom.:

69657

AF XY:

0.748

AC XY:

101599

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.809

Gnomad AMR exome

AF:

0.580

Gnomad ASJ exome

AF:

0.775

Gnomad EAS exome

AF:

0.582

Gnomad SAS exome

AF:

0.778

Gnomad FIN exome

AF:

0.760

Gnomad NFE exome

AF:

0.784

Gnomad OTH exome

AF:

0.752

GnomAD4 exome

AF:

0.772

AC:

1128457

AN:

1461882

Hom.:

438172

Cov.:

106

AF XY:

0.773

AC XY:

562249

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.808

Gnomad4 AMR exome

AF:

0.586

Gnomad4 ASJ exome

AF:

0.772

Gnomad4 EAS exome

AF:

0.535

Gnomad4 SAS exome

AF:

0.777

Gnomad4 FIN exome

AF:

0.756

Gnomad4 NFE exome

AF:

0.788

Gnomad4 OTH exome

AF:

0.770

GnomAD4 genome

AF:

0.768

AC:

116905

AN:

152150

Hom.:

45183

Cov.:

AF XY:

0.765

AC XY:

56891

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.805

Gnomad4 AMR

AF:

0.653

Gnomad4 ASJ

AF:

0.762

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.780

Gnomad4 FIN

AF:

0.759

Gnomad4 NFE

AF:

0.788

Gnomad4 OTH

AF:

0.768

Alfa

AF:

0.780

Hom.:

14706

Bravo

AF:

0.760

TwinsUK

AF:

0.789

AC:

2927

ALSPAC

AF:

0.786

AC:

3028

ESP6500AA

AF:

0.813

AC:

3581

ESP6500EA

AF:

0.784

AC:

6746

ExAC

AF:

0.745

AC:

90441

Asia WGS

AF:

0.708

AC:

2461

AN:

3478

EpiCase

AF:

0.783

EpiControl

AF:

0.792

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.19

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0000050

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.13

Sift

Benign

0.091

Sift4G

Benign

0.093

Polyphen

0.25

Vest4

0.052

MutPred

0.51

Gain of disorder (P = 0.0459);

MPC

0.068

ClinPred

0.072

GERP RS

3.9

Varity_R

0.55

gMVP

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over