rs2246775

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBF1	NM_001377137.1	c.163+37378A>C		intron_variant		ENST00000369983.5	NP_001364066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBF1	ENST00000369983.5	c.163+37378A>C		intron_variant		1	NM_001377137.1	ENSP00000359000.4

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

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.355

Alfa AF: 0.256 Hom.: 824

Bravo AF: 0.321

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.83

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

LitVar

Other links and lift over

dbSNP: rs2246775; hg19: chr10-104057251;