11-18526999-A-G

Variant names:

• chr11-18526999-A-G
• rs2292179
• ENST00000690266.2:n.43A>G

Variant summary

Our verdict is Benign. The variant received -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: ENSG00000289499 ENST00000690266.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958
• Publications: 7 publications found

Genes affected

ENSG00000289499 (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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000690266.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSG101	NM_006292.4	MANE Select	c.-183T>C		upstream_gene	N/A	NP_006283.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289499	ENST00000690266.2		n.43A>G		non_coding_transcript_exon	Exon 1 of 1
	TSG101	ENST00000251968.4	TSL:1 MANE Select	c.-183T>C		upstream_gene	N/A	ENSP00000251968.3
	TSG101	ENST00000438874.6	TSL:1	n.-100T>C		upstream_gene	N/A

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

African (AFR) AF: 0.0314 AC: 436 AN: 13890

American (AMR) AF: 0.188 AC: 3709 AN: 19774

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 1813 AN: 14262

East Asian (EAS) AF: 0.258 AC: 7825 AN: 30298

South Asian (SAS) AF: 0.230 AC: 11345 AN: 49386

European-Finnish (FIN) AF: 0.186 AC: 5506 AN: 29556

Middle Eastern (MID) AF: 0.151 AC: 559 AN: 3692

European-Non Finnish (NFE) AF: 0.122 AC: 41756 AN: 343400

Other (OTH) AF: 0.140 AC: 4028 AN: 28692

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

African (AFR) AF: 0.0330 AC: 1370 AN: 41566

American (AMR) AF: 0.143 AC: 2184 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3466

East Asian (EAS) AF: 0.219 AC: 1128 AN: 5160

South Asian (SAS) AF: 0.238 AC: 1149 AN: 4820

European-Finnish (FIN) AF: 0.213 AC: 2251 AN: 10580

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8210 AN: 68002

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.0602 Hom.: 69

Bravo AF: 0.104

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.59
PhyloP100		-0.96
PromoterAI		-0.010	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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