chr11-18526636-T-G

Variant names:

• chr11-18526636-T-G
• rs1395319
• NM_006292.4:c.42+139A>C

Variant summary

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

The NM_006292.4(TSG101):​c.42+139A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 994,868 control chromosomes in the GnomAD database, including 71,359 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 0.37 (10818 hom., cov: 33)
  • Exomes 𝑓: 0.37 (60541 hom.)
• Consequence: TSG101 NM_006292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

Genes affected

TSG101 (HGNC:15971): (tumor susceptibility 101) The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSG101	NM_006292.4	c.42+139A>C		intron_variant	Intron 1 of 9	ENST00000251968.4	NP_006283.1
TSG101	XM_005253108.5	c.-157+139A>C		intron_variant	Intron 1 of 10		XP_005253165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSG101	ENST00000251968.4	c.42+139A>C		intron_variant	Intron 1 of 9	1	NM_006292.4	ENSP00000251968.3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55788 AN: 151824 Hom.: 10788 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.367 AC: 309568 AN: 842926 Hom.: 60541 AF XY: 0.373 AC XY: 157745 AN XY: 423092

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.368 AC: 55857 AN: 151942 Hom.: 10818 Cov.: 33 AF XY: 0.376 AC XY: 27950 AN XY: 74270

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.384

Alfa AF: 0.350 Hom.: 1221

Bravo AF: 0.365

Asia WGS AF: 0.627 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1395319; hg19: chr11-18548183;