Variant 1-89056855-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002053.3(GBP1):c.1154C>T(p.Ala385Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

GBP1
NM_002053.3 missense, splice_region

Scores

Splicing: ADA: 0.001362

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.32

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03889203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBP1	NM_002053.3 link	c.1154C>T	p.Ala385Val	missense_variant, splice_region_variant	Exon 7 of 11	ENST00000370473.5	NP_002044.2	P32455
LOC105378841	XR_947575.3 link	n.3207+9935G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GBP1	ENST00000370473.5 link	c.1154C>T	p.Ala385Val	missense_variant, splice_region_variant	Exon 7 of 11	1	NM_002053.3	ENSP00000359504.4	P32455
GBP1	ENST00000459831.2 link	n.1980C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 6 of 10	3
GBP1	ENST00000495131.2 link	n.1374C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 7 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250066

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000684

AC:

AN:

1461376

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1154C>T (p.A385V) alteration is located in exon 7 (coding exon 6) of the GBP1 gene. This alteration results from a C to T substitution at nucleotide position 1154, causing the alanine (A) at amino acid position 385 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.5

DANN

Benign

0.27

DEOGEN2

Benign

0.026

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.15

M_CAP

Benign

0.0060

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.72

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.016

Sift

Benign

0.80

Sift4G

Benign

0.51

Polyphen

0.043

Vest4

0.19

MVP

0.17

MPC

0.22

ClinPred

0.033

GERP RS

-9.6

Varity_R

0.14

gMVP

0.079

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.044

SpliceAI score (max)

0.47

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.47

Position offset: 6

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