rs1057050

Positions:

• chr10-102382537-G-A
• chr10-102382537-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377137.1(GBF1):​c.*201G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 533,422 control chromosomes in the GnomAD database, including 729 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 0.047 (220 hom., cov: 31)
  • Exomes 𝑓: 0.048 (509 hom.)
• Consequence: GBF1 NM_001377137.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBF1	NM_001377137.1	c.*201G>A		3_prime_UTR_variant	40/40	ENST00000369983.5	NP_001364066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBF1	ENST00000369983.5	c.*201G>A		3_prime_UTR_variant	40/40	1	NM_001377137.1	ENSP00000359000	P4

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7172 AN: 152156 Hom.: 219 Cov.: 31

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.0482

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.0475 AC: 18116 AN: 381148 Hom.: 509 Cov.: 4 AF XY: 0.0467 AC XY: 9309 AN XY: 199158

Gnomad4 AFR exome AF: 0.0310

Gnomad4 AMR exome AF: 0.0418

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.000262

Gnomad4 SAS exome AF: 0.0294

Gnomad4 FIN exome AF: 0.0372

Gnomad4 NFE exome AF: 0.0597

Gnomad4 OTH exome AF: 0.0443

GnomAD4 genome AF: 0.0472 AC: 7183 AN: 152274 Hom.: 220 Cov.: 31 AF XY: 0.0462 AC XY: 3441 AN XY: 74452

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.0602

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0502 Hom.: 305

Bravo AF: 0.0480

Asia WGS AF: 0.0290 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1057050; hg19: chr10-104142294;