rs4963060

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000317204.11(TOLLIP):​c.34-4036C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,138 control chromosomes in the GnomAD database, including 5,007 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 0.25 ( 5007 hom., cov: 33)

Consequence

TOLLIP
ENST00000317204.11 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.618
Variant links:
Genes affected
TOLLIP (HGNC:16476): (toll interacting protein) This gene encodes a ubiquitin-binding protein that interacts with several Toll-like receptor (TLR) signaling cascade components. The encoded protein regulates inflammatory signaling and is involved in interleukin-1 receptor trafficking and in the turnover of IL1R-associated kinase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TOLLIPNM_019009.4 linkuse as main transcriptc.34-4036C>T intron_variant ENST00000317204.11 NP_061882.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TOLLIPENST00000317204.11 linkuse as main transcriptc.34-4036C>T intron_variant 1 NM_019009.4 ENSP00000314733 P1Q9H0E2-1

Frequencies

GnomAD3 genomes
AF:
0.247
AC:
37565
AN:
152020
Hom.:
5008
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.194
Gnomad AMI
AF:
0.260
Gnomad AMR
AF:
0.204
Gnomad ASJ
AF:
0.299
Gnomad EAS
AF:
0.0178
Gnomad SAS
AF:
0.231
Gnomad FIN
AF:
0.198
Gnomad MID
AF:
0.304
Gnomad NFE
AF:
0.312
Gnomad OTH
AF:
0.255
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.247
AC:
37565
AN:
152138
Hom.:
5007
Cov.:
33
AF XY:
0.239
AC XY:
17755
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.193
Gnomad4 AMR
AF:
0.203
Gnomad4 ASJ
AF:
0.299
Gnomad4 EAS
AF:
0.0178
Gnomad4 SAS
AF:
0.231
Gnomad4 FIN
AF:
0.198
Gnomad4 NFE
AF:
0.312
Gnomad4 OTH
AF:
0.251
Alfa
AF:
0.235
Hom.:
962
Bravo
AF:
0.244
Asia WGS
AF:
0.128
AC:
446
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
3.3
DANN
Benign
0.94

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4963060; hg19: chr11-1321060; API