rs3758549

Variant names:

• chr10-102244438-G-A
• rs3758549
• NM_001391923.1:c.-11+13522G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-102244438-G-A
• chr10-102244438-G-C
• chr10-102244438-G-T

Variant summary

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

The NM_001391923.1(GBF1):​c.-11+13522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,138 control chromosomes in the GnomAD database, including 1,895 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 0.14 (1895 hom., cov: 32)
• Consequence: GBF1 NM_001391923.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• Publications: 27 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBF1	NM_001391923.1	c.-11+13522G>A		intron_variant	Intron 1 of 39		NP_001378852.1
GBF1	NM_001391924.1	c.-148-1206G>A		intron_variant	Intron 1 of 40		NP_001378853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21798 AN: 152022 Hom.: 1899 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.143 AC: 21799 AN: 152138 Hom.: 1895 Cov.: 32 AF XY: 0.143 AC XY: 10618 AN XY: 74370

African (AFR) AF: 0.0487 AC: 2020 AN: 41514

American (AMR) AF: 0.134 AC: 2057 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3468

East Asian (EAS) AF: 0.148 AC: 767 AN: 5186

South Asian (SAS) AF: 0.0868 AC: 419 AN: 4828

European-Finnish (FIN) AF: 0.213 AC: 2249 AN: 10562

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.196 AC: 13334 AN: 67966

Other (OTH) AF: 0.152 AC: 321 AN: 2116

Alfa AF: 0.178 Hom.: 5411

Bravo AF: 0.133

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.4
DANN	Benign	0.45
PhyloP100		0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3758549; hg19: chr10-104004195;