rs2246775

Variant names:

• chr10-102297494-A-C
• rs2246775
• NM_001377137.1:c.163+37378A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-102297494-A-C
• chr10-102297494-A-G
• chr10-102297494-A-T

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+37378A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,206 control chromosomes in the GnomAD database, including 8,848 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 0.33 (8848 hom., cov: 33)
• Consequence: GBF1 NM_001377137.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 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+37378A>C		intron	N/A	NP_001364066.1
	GBF1	NM_001411027.1		c.163+37378A>C		intron	N/A	NP_001397956.1
	GBF1	NM_001391922.1		c.163+37378A>C		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+37378A>C		intron	N/A	ENSP00000359000.4
	GBF1	ENST00000673650.1		c.163+37378A>C		intron	N/A	ENSP00000501233.1
	GBF1	ENST00000674034.1		c.163+37378A>C		intron	N/A	ENSP00000501064.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49853 AN: 152088 Hom.: 8847 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.328 AC: 49853 AN: 152206 Hom.: 8848 Cov.: 33 AF XY: 0.331 AC XY: 24662 AN XY: 74416

African (AFR) AF: 0.187 AC: 7767 AN: 41536

American (AMR) AF: 0.381 AC: 5830 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1302 AN: 5186

South Asian (SAS) AF: 0.484 AC: 2330 AN: 4816

European-Finnish (FIN) AF: 0.381 AC: 4026 AN: 10566

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25930 AN: 68010

Other (OTH) AF: 0.355 AC: 752 AN: 2116

Alfa AF: 0.253 Hom.: 841

Bravo AF: 0.321

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		1.8
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: rs2246775; hg19: chr10-104057251;