10-102359367-C-T

Position:

• chr10-102359367-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2 BP4_Moderate BS2

The NM_001377137.1(GBF1):​c.1112C>T​(p.Ala371Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,460,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: GBF1 NM_001377137.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86

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 Likely_benign. Variant got -5 ACMG points.

• PP2: Missense variant where missense usually causes diseases, GBF1
• BP4: Computational evidence support a benign effect (MetaRNN=0.23454225).
• BS2: High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBF1	NM_001377137.1	c.1112C>T	p.Ala371Val	missense_variant	11/40	ENST00000369983.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBF1	ENST00000369983.5	c.1112C>T	p.Ala371Val	missense_variant	11/40	1	NM_001377137.1	P4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1460744 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 726754

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.039	D
Sift4G	Benign	0.30	T
Polyphen		0.80	P
Vest4		0.41
MutPred		0.14		Gain of helix (P = 0.0425);
MVP		0.35
MPC		0.22
ClinPred		0.70	D
GERP RS		5.6
Varity_R		0.11
gMVP		0.33

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: rs1003880241; hg19: chr10-104119124;