chr11-18526999-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000690266.2(ENSG00000289499):​n.43A>C 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 0.00000187 in 533,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: ENSG00000289499 ENST00000690266.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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>G		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>C		non_coding_transcript_exon	Exon 1 of 1
	TSG101	ENST00000251968.4	TSL:1 MANE Select	c.-183T>G		upstream_gene	N/A	ENSP00000251968.3
	TSG101	ENST00000438874.6	TSL:1	n.-100T>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000187 AC: 1 AN: 533420 Hom.: 0 Cov.: 7 AF XY: 0.00000360 AC XY: 1 AN XY: 277504

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13892

American (AMR) AF: 0.00 AC: 0 AN: 19806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14268

East Asian (EAS) AF: 0.00 AC: 0 AN: 30328

South Asian (SAS) AF: 0.0000202 AC: 1 AN: 49436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 343694

Other (OTH) AF: 0.00 AC: 0 AN: 28728

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.98
DANN	Benign	0.55
PhyloP100		-0.96
PromoterAI		0.0082	Neutral

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;