11-18481612-C-T

Position:

• chr11-18481612-C-T

Variant summary

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

The NM_006292.4(TSG101):​c.1083+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,601,702 control chromosomes in the GnomAD database, including 31,327 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 0.17 (2666 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28661 hom.)
• Consequence: TSG101 NM_006292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSG101	NM_006292.4	c.1083+18G>A		intron_variant		ENST00000251968.4
TSG101	XM_005253108.5	c.927+18G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSG101	ENST00000251968.4	c.1083+18G>A		intron_variant		1	NM_006292.4	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25295 AN: 152048 Hom.: 2644 Cov.: 32

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.179

GnomAD3 exomes AF: 0.223 AC: 54166 AN: 243288 Hom.: 7199 AF XY: 0.224 AC XY: 29390 AN XY: 131296

Gnomad AFR exome AF: 0.0839

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.142

Gnomad EAS exome AF: 0.412

Gnomad SAS exome AF: 0.316

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.186 AC: 269407 AN: 1449536 Hom.: 28661 Cov.: 33 AF XY: 0.188 AC XY: 135610 AN XY: 719568

Gnomad4 AFR exome AF: 0.0851

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.167 AC: 25343 AN: 152166 Hom.: 2666 Cov.: 32 AF XY: 0.178 AC XY: 13267 AN XY: 74372

Gnomad4 AFR AF: 0.0866

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.188

Alfa AF: 0.158 Hom.: 2981

Bravo AF: 0.155

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.64

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: rs2279900; hg19: chr11-18503159; COSMIC: COSV52653140; COSMIC: COSV52653140;