rs8018

Variant names:

• chr11-18481759-G-A
• rs8018
• NM_006292.4:c.954C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006292.4(TSG101):​c.954C>T​(p.Ile318Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 1,614,136 control chromosomes in the GnomAD database, including 281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (145 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (136 hom.)
• Consequence: TSG101 NM_006292.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.01
• Publications: 5 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 11-18481759-G-A is Benign according to our data. Variant chr11-18481759-G-A is described in ClinVar as Benign. ClinVar VariationId is 774621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0792 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.954C>T	p.Ile318Ile	synonymous	Exon 9 of 10	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.954C>T	p.Ile318Ile	synonymous	Exon 9 of 10	ENSP00000251968.3	Q99816-1
	TSG101	ENST00000860304.1		c.1056C>T	p.Ile352Ile	synonymous	Exon 10 of 11	ENSP00000530363.1
	TSG101	ENST00000860307.1		c.1047C>T	p.Ile349Ile	synonymous	Exon 10 of 11	ENSP00000530366.1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3626 AN: 152168 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00936

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000852

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.00626 AC: 1573 AN: 251394 AF XY: 0.00449

Gnomad AFR exome AF: 0.0797

Gnomad AMR exome AF: 0.00529

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000607

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00275 AC: 4023 AN: 1461850 Hom.: 136 Cov.: 32 AF XY: 0.00243 AC XY: 1764 AN XY: 727226

African (AFR) AF: 0.0848 AC: 2839 AN: 33478

American (AMR) AF: 0.00561 AC: 251 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86250

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53414

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5768

European-Non Finnish (NFE) AF: 0.000452 AC: 503 AN: 1112002

Other (OTH) AF: 0.00606 AC: 366 AN: 60394

GnomAD4 genome AF: 0.0238 AC: 3630 AN: 152286 Hom.: 145 Cov.: 32 AF XY: 0.0230 AC XY: 1710 AN XY: 74482

African (AFR) AF: 0.0815 AC: 3385 AN: 41538

American (AMR) AF: 0.00935 AC: 143 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000853 AC: 58 AN: 68030

Other (OTH) AF: 0.0185 AC: 39 AN: 2110

Alfa AF: 0.0115 Hom.: 49

Bravo AF: 0.0275

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		2.0
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs8018; hg19: chr11-18503306;