rs2292179

Positions:

• chr11-18526999-A-G
• chr11-18526999-A-T

Variant summary

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

The ENST00000690266.2(ENSG00000289499):​n.43A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 685,162 control chromosomes in the GnomAD database, including 7,645 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 0.11 (1222 hom., cov: 33)
  • Exomes 𝑓: 0.14 (6423 hom.)
• Consequence: ENST00000690266.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958

Genes affected

(HGNC:):

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000690266.2	n.43A>G		non_coding_transcript_exon_variant	1/1
TSG101	ENST00000536719.5			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17099 AN: 152094 Hom.: 1209 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.144 AC: 76977 AN: 532950 Hom.: 6423 Cov.: 7 AF XY: 0.148 AC XY: 41010 AN XY: 277256

Gnomad4 AFR exome AF: 0.0314

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.113 AC: 17132 AN: 152212 Hom.: 1222 Cov.: 33 AF XY: 0.120 AC XY: 8934 AN XY: 74408

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0614 Hom.: 69

Bravo AF: 0.104

Asia WGS AF: 0.257 AC: 892 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	2.0
DANN	Benign	0.59

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: rs2292179; hg19: chr11-18548546; COSMIC: COSV52652901; COSMIC: COSV52652901;