Genetic Variant GBF1:c.*201G>A (chr10-102382537-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.*201G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 533,422 control chromosomes in the GnomAD database, including 729 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 0.047 ( 220 hom., cov: 31)

Exomes 𝑓: 0.048 ( 509 hom. )

Consequence

GBF1
NM_001377137.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.219

Publications

14 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0587 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.*201G>A	3_prime_UTR	Exon 40 of 40	NP_001364066.1	Q92538-4
GBF1	NM_001411027.1		c.*201G>A	3_prime_UTR	Exon 41 of 41	NP_001397956.1	A0A669KBG8
GBF1	NM_001391922.1		c.*201G>A	3_prime_UTR	Exon 41 of 41	NP_001378851.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GBF1	ENST00000369983.5	TSL:1 MANE Select	c.*201G>A		3_prime_UTR	Exon 40 of 40	ENSP00000359000.4	Q92538-4
GBF1	ENST00000679080.1		c.383G>A	p.Arg128His	missense	Exon 2 of 2	ENSP00000503258.1	A0A7I2V350
GBF1	ENST00000673650.1		c.*201G>A		3_prime_UTR	Exon 41 of 41	ENSP00000501233.1	A0A669KBG8

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7172

AN:

152156

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.0482

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0602

Gnomad OTH

AF:

0.0368

GnomAD4 exome

AF:

0.0475

AC:

18116

AN:

381148

Hom.:

509

Cov.:

AF XY:

0.0467

AC XY:

9309

AN XY:

199158

show subpopulations

African (AFR)

AF:

0.0310

AC:

328

AN:

10568

American (AMR)

AF:

0.0418

AC:

518

AN:

12384

Ashkenazi Jewish (ASJ)

AF:

0.0149

AC:

184

AN:

12366

East Asian (EAS)

AF:

0.000262

AC:

AN:

26678

South Asian (SAS)

AF:

0.0294

AC:

914

AN:

31130

European-Finnish (FIN)

AF:

0.0372

AC:

1002

AN:

26934

Middle Eastern (MID)

AF:

0.0185

AC:

AN:

1786

European-Non Finnish (NFE)

AF:

0.0597

AC:

14119

AN:

236494

Other (OTH)

AF:

0.0443

AC:

1011

AN:

22808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

844

1688

2531

3375

4219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0472

AC:

7183

AN:

152274

Hom.:

220

Cov.:

AF XY:

0.0462

AC XY:

3441

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0339

AC:

1408

AN:

41566

American (AMR)

AF:

0.0484

AC:

740

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3472

East Asian (EAS)

AF:

0.000966

AC:

AN:

5176

South Asian (SAS)

AF:

0.0257

AC:

124

AN:

4828

European-Finnish (FIN)

AF:

0.0340

AC:

361

AN:

10604

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0602

AC:

4097

AN:

68018

Other (OTH)

AF:

0.0398

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

346

692

1039

1385

1731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0494

Hom.:

434

Bravo

AF:

0.0480

Asia WGS

AF:

0.0290

AC:

104

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.6

(source)

DANN

Benign

0.59

PhyloP100

-0.22

PromoterAI

-0.0098

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over