Genetic Variant TSG101:c.1083+18G>A (chr11-18481612-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.256

Publications

8 publications found

Variant links:

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]

TSG101 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSG101	NM_006292.4 link	c.1083+18G>A		intron_variant	Intron 9 of 9	ENST00000251968.4	NP_006283.1	Q99816-1
TSG101	XM_005253108.5 link	c.927+18G>A		intron_variant	Intron 10 of 10		XP_005253165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSG101	ENST00000251968.4 link	c.1083+18G>A		intron_variant	Intron 9 of 9	1	NM_006292.4	ENSP00000251968.3		Q99816-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25295

AN:

152048

Hom.:

2644

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.188

AC XY:

135610

AN XY:

719568

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

10945

21890

32836

43781

54726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6710

13420

20130

26840

33550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.167

AC:

25343

AN:

152166

Hom.:

2666

Cov.:

AF XY:

0.178

AC XY:

13267

AN XY:

74372

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10884

AN:

67998

Other (OTH)

AF:

0.188

AC:

397

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1022

2045

3067

4090

5112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.0

(source)

DANN

Benign

0.64

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over