chr11-18481612-C-T

Variant names:

• chr11-18481612-C-T
• rs2279900
• NM_006292.4:c.1083+18G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006292.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSG101	NM_006292.4	MANE Select	c.1083+18G>A		intron	N/A	NP_006283.1	Q99816-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSG101	ENST00000251968.4	TSL:1 MANE Select	c.1083+18G>A		intron	N/A	ENSP00000251968.3	Q99816-1
	TSG101	ENST00000860304.1		c.1185+18G>A		intron	N/A	ENSP00000530363.1
	TSG101	ENST00000860307.1		c.1176+18G>A		intron	N/A	ENSP00000530366.1

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

GnomAD2 exomes AF: 0.223 AC: 54166 AN: 243288 AF XY: 0.224

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 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

African (AFR) AF: 0.0851 AC: 2797 AN: 32860

American (AMR) AF: 0.265 AC: 11308 AN: 42598

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3660 AN: 25652

East Asian (EAS) AF: 0.450 AC: 17764 AN: 39516

South Asian (SAS) AF: 0.314 AC: 26429 AN: 84106

European-Finnish (FIN) AF: 0.295 AC: 15677 AN: 53138

Middle Eastern (MID) AF: 0.173 AC: 984 AN: 5696

European-Non Finnish (NFE) AF: 0.162 AC: 179299 AN: 1106104

Other (OTH) AF: 0.192 AC: 11489 AN: 59866

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

African (AFR) AF: 0.0866 AC: 3596 AN: 41528

American (AMR) AF: 0.186 AC: 2851 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2108 AN: 5170

South Asian (SAS) AF: 0.332 AC: 1604 AN: 4828

European-Finnish (FIN) AF: 0.312 AC: 3294 AN: 10554

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10884 AN: 67998

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.158 Hom.: 3683

Bravo AF: 0.155

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.64
PhyloP100		0.26
Mutation Taster		=100/0	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: rs2279900; hg19: chr11-18503159; COSMIC: COSV52653140; COSMIC: COSV52653140;