3-100709442-G-T

Variant names:

• chr3-100709442-G-T
• rs72919417
• ENST00000675692:c.-323G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001007565.2(TFG):​c.-44+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 152,636 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (110 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (0 hom.)
• Consequence: TFG NM_001007565.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.80

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-100709442-G-T is Benign according to our data. Variant chr3-100709442-G-T is described in ClinVar as [Benign]. Clinvar id is 378883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFG	NM_001007565.2	c.-44+11G>T		intron_variant	Intron 1 of 7		NP_001007566.1
TFG	XM_005247066.3	c.-44+11G>T		intron_variant	Intron 1 of 7		XP_005247123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFG	ENST00000675692	c.-323G>T		5_prime_UTR_variant	Exon 1 of 9			ENSP00000502034.1
TFG	ENST00000675553	c.-190G>T		5_prime_UTR_variant	Exon 1 of 8			ENSP00000501815.1
TFG	ENST00000674645	c.-323G>T		5_prime_UTR_variant	Exon 1 of 8			ENSP00000501892.1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3617 AN: 152208 Hom.: 109 Cov.: 33

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00669

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00523

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00321 AC: 1 AN: 312 Hom.: 0 Cov.: 0 AF XY: 0.00435 AC XY: 1 AN XY: 230

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00370

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0238 AC: 3623 AN: 152324 Hom.: 110 Cov.: 33 AF XY: 0.0232 AC XY: 1728 AN XY: 74482

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00669

Gnomad4 NFE AF: 0.00523

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00598 Hom.: 3

Bravo AF: 0.0277

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Apr 26, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.0020
DANN	Benign	0.48

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: rs72919417; hg19: chr3-100428286;