rs1541046

Variant names:

• chr10-102245629-G-A
• rs1541046
• NM_001377137.1:c.-163G>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.-163G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,116 control chromosomes in the GnomAD database, including 33,352 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 0.66 (33347 hom., cov: 32)
  • Exomes 𝑓: 0.57 (5 hom.)
• Consequence: GBF1 NM_001377137.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 10 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBF1	NM_001377137.1	c.-163G>A		5_prime_UTR_variant	Exon 1 of 40	ENST00000369983.5	NP_001364066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBF1	ENST00000369983.5	c.-163G>A		5_prime_UTR_variant	Exon 1 of 40	1	NM_001377137.1	ENSP00000359000.4

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99995 AN: 151956 Hom.: 33292 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.571 AC: 24 AN: 42 Hom.: 5 Cov.: 0 AF XY: 0.611 AC XY: 22 AN XY: 36

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.583 AC: 21 AN: 36

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.658 AC: 100109 AN: 152074 Hom.: 33347 Cov.: 32 AF XY: 0.655 AC XY: 48707 AN XY: 74342

African (AFR) AF: 0.764 AC: 31695 AN: 41504

American (AMR) AF: 0.614 AC: 9388 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2044 AN: 3468

East Asian (EAS) AF: 0.748 AC: 3856 AN: 5158

South Asian (SAS) AF: 0.518 AC: 2493 AN: 4816

European-Finnish (FIN) AF: 0.620 AC: 6541 AN: 10554

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42050 AN: 67974

Other (OTH) AF: 0.633 AC: 1334 AN: 2108

Alfa AF: 0.623 Hom.: 48290

Bravo AF: 0.663

Asia WGS AF: 0.638 AC: 2220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		1.0
PromoterAI		-0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	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: rs1541046; hg19: chr10-104005386;