Genetic Variant GBF1:c.-163G>A (chr10-102245629-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001377137.1(GBF1):c.-163G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,116 control chromosomes in the GnomAD database, including 33,352 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 33347 hom., cov: 32)

Exomes 𝑓: 0.57 ( 5 hom. )

Consequence

GBF1
NM_001377137.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Publications

10 publications found

Variant links:

Genes affected

GBF1 (HGNC:4181): (golgi brefeldin A resistant guanine nucleotide exchange factor 1) This gene encodes a member of the Sec7 domain family. The encoded protein is a guanine nucleotide exchange factor that regulates the recruitment of proteins to membranes by mediating GDP to GTP exchange. The encoded protein is localized to the Golgi apparatus and plays a role in vesicular trafficking by activating ADP ribosylation factor 1. The encoded protein has also been identified as an important host factor for viral replication. Multiple transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

GBF1 Gene-Disease associations (from GenCC):

axonal neuropathy
Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox

GBF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377137.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GBF1	NM_001377137.1	MANE Select	c.-163G>A	5_prime_UTR	Exon 1 of 40	NP_001364066.1	Q92538-4
GBF1	NM_001411027.1		c.-163G>A	5_prime_UTR	Exon 1 of 41	NP_001397956.1	A0A669KBG8
GBF1	NM_001391922.1		c.-163G>A	5_prime_UTR	Exon 1 of 41	NP_001378851.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GBF1	ENST00000369983.5	TSL:1 MANE Select	c.-163G>A	5_prime_UTR	Exon 1 of 40	ENSP00000359000.4	Q92538-4
GBF1	ENST00000673650.1		c.-163G>A	5_prime_UTR	Exon 1 of 41	ENSP00000501233.1	A0A669KBG8
GBF1	ENST00000674034.1		c.-163G>A	5_prime_UTR	Exon 1 of 41	ENSP00000501064.1	A0A669KB10

Frequencies

GnomAD3 genomes

AF:

0.658

AC:

99995

AN:

151956

Hom.:

33292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.763

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.518

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.628

GnomAD4 exome

AF:

0.571

AC:

AN:

Hom.:

Cov.:

AF XY:

0.611

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.583

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.658

AC:

100109

AN:

152074

Hom.:

33347

Cov.:

AF XY:

0.655

AC XY:

48707

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.764

AC:

31695

AN:

41504

American (AMR)

AF:

0.614

AC:

9388

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

2044

AN:

3468

East Asian (EAS)

AF:

0.748

AC:

3856

AN:

5158

South Asian (SAS)

AF:

0.518

AC:

2493

AN:

4816

European-Finnish (FIN)

AF:

0.620

AC:

6541

AN:

10554

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.619

AC:

42050

AN:

67974

Other (OTH)

AF:

0.633

AC:

1334

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1749

3498

5247

6996

8745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.623

Hom.:

48290

Bravo

AF:

0.663

Asia WGS

AF:

0.638

AC:

2220

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

1.0

PromoterAI

-0.20

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over