rs591728

Positions:

• chr3-100714748-T-C

Variant summary

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

The NM_006070.6(TFG):​c.184+879T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,094 control chromosomes in the GnomAD database, including 5,417 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 0.24 (5417 hom., cov: 33)
• Consequence: TFG NM_006070.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

Genes affected

TFG (HGNC:11758): (trafficking from ER to golgi regulator) There are several documented fusion oncoproteins encoded partially by this gene. This gene also participates in several oncogenic rearrangements resulting in anaplastic lymphoma and mixoid chondrosarcoma, and may play a role in the NF-kappaB pathway. Multiple transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFG	NM_006070.6	c.184+879T>C		intron_variant		ENST00000240851.9	NP_006061.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFG	ENST00000240851.9	c.184+879T>C		intron_variant		1	NM_006070.6	ENSP00000240851	P4

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37063 AN: 151976 Hom.: 5425 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.244 AC: 37048 AN: 152094 Hom.: 5417 Cov.: 33 AF XY: 0.239 AC XY: 17772 AN XY: 74346

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.259

Alfa AF: 0.302 Hom.: 3456

Bravo AF: 0.233

Asia WGS AF: 0.0870 AC: 305 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.87

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: rs591728; hg19: chr3-100433592;