11-18482190-A-G

Variant names:

• chr11-18482190-A-G
• rs3781640
• NM_006292.4:c.844-321T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000251968.4(TSG101):​c.844-321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,276 control chromosomes in the GnomAD database, including 1,229 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 (1229 hom., cov: 32)
• Consequence: TSG101 ENST00000251968.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 6 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 (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000251968.4. 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.844-321T>C		intron	N/A	NP_006283.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSG101	ENST00000251968.4	TSL:1 MANE Select	c.844-321T>C		intron	N/A	ENSP00000251968.3
	TSG101	ENST00000536719.5	TSL:5	c.844-321T>C		intron	N/A	ENSP00000438471.1
	TSG101	ENST00000540555.1	TSL:2	n.193-321T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17179 AN: 152158 Hom.: 1221 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.135

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.113 AC: 17194 AN: 152276 Hom.: 1229 Cov.: 32 AF XY: 0.120 AC XY: 8950 AN XY: 74440

African (AFR) AF: 0.0302 AC: 1254 AN: 41582

American (AMR) AF: 0.144 AC: 2200 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3472

East Asian (EAS) AF: 0.218 AC: 1130 AN: 5180

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4828

European-Finnish (FIN) AF: 0.212 AC: 2244 AN: 10586

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8344 AN: 68012

Other (OTH) AF: 0.140 AC: 295 AN: 2114

Alfa AF: 0.125 Hom.: 2173

Bravo AF: 0.105

Asia WGS AF: 0.251 AC: 873 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	0.81
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3781640; hg19: chr11-18503737;