rs7902537

Variant names:

• chr10-102282852-G-A
• rs7902537
• NM_001377137.1:c.163+22736G>A

Variant summary

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

The NM_001377137.1(GBF1):​c.163+22736G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 152,222 control chromosomes in the GnomAD database, including 479 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 0.054 (479 hom., cov: 32)
• Consequence: GBF1 NM_001377137.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBF1	NM_001377137.1	MANE Select	c.163+22736G>A		intron	N/A	NP_001364066.1
	GBF1	NM_001411027.1		c.163+22736G>A		intron	N/A	NP_001397956.1
	GBF1	NM_001391922.1		c.163+22736G>A		intron	N/A	NP_001378851.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBF1	ENST00000369983.5	TSL:1 MANE Select	c.163+22736G>A		intron	N/A	ENSP00000359000.4
	GBF1	ENST00000673650.1		c.163+22736G>A		intron	N/A	ENSP00000501233.1
	GBF1	ENST00000674034.1		c.163+22736G>A		intron	N/A	ENSP00000501064.1

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8268 AN: 152104 Hom.: 477 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0503

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

GnomAD4 genome AF: 0.0545 AC: 8295 AN: 152222 Hom.: 479 Cov.: 32 AF XY: 0.0521 AC XY: 3880 AN XY: 74450

African (AFR) AF: 0.146 AC: 6052 AN: 41504

American (AMR) AF: 0.0307 AC: 469 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0355 AC: 123 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0298 AC: 144 AN: 4828

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10620

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0198 AC: 1349 AN: 68006

Other (OTH) AF: 0.0498 AC: 105 AN: 2108

Alfa AF: 0.0431 Hom.: 48

Bravo AF: 0.0603

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.19
PhyloP100		-0.17
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: rs7902537; hg19: chr10-104042609;