rs1890060

Variant names:

• chr10-102363085-A-G
• rs1890060
• NM_001377137.1:c.1877-171A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377137.1(GBF1):​c.1877-171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,120 control chromosomes in the GnomAD database, including 3,551 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 0.21 (3551 hom., cov: 31)
• Consequence: GBF1 NM_001377137.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 7 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBF1	NM_001377137.1	c.1877-171A>G		intron_variant	Intron 15 of 39	ENST00000369983.5	NP_001364066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBF1	ENST00000369983.5	c.1877-171A>G		intron_variant	Intron 15 of 39	1	NM_001377137.1	ENSP00000359000.4

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31792 AN: 152002 Hom.: 3548 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31795 AN: 152120 Hom.: 3551 Cov.: 31 AF XY: 0.213 AC XY: 15828 AN XY: 74384

African (AFR) AF: 0.148 AC: 6145 AN: 41506

American (AMR) AF: 0.266 AC: 4064 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3468

East Asian (EAS) AF: 0.109 AC: 565 AN: 5170

South Asian (SAS) AF: 0.319 AC: 1540 AN: 4822

European-Finnish (FIN) AF: 0.270 AC: 2857 AN: 10566

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15176 AN: 67978

Other (OTH) AF: 0.213 AC: 450 AN: 2110

Alfa AF: 0.231 Hom.: 2178

Bravo AF: 0.206

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.36
PhyloP100		-0.021
PromoterAI		0.0070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1890060; hg19: chr10-104122842; COSMIC: COSV64144538; COSMIC: COSV64144538;