rs5743905

Positions:

• chr11-1301483-G-C
• chr11-1301483-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019009.4(TOLLIP):​c.34-5689C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 151,796 control chromosomes in the GnomAD database, including 338 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 0.062 (338 hom., cov: 28)
• Consequence: TOLLIP NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOLLIP	NM_019009.4	c.34-5689C>G		intron_variant		ENST00000317204.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOLLIP	ENST00000317204.11	c.34-5689C>G		intron_variant		1	NM_019009.4	P1

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9372 AN: 151678 Hom.: 338 Cov.: 28

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0497

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0515

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

GnomAD4 genome AF: 0.0618 AC: 9376 AN: 151796 Hom.: 338 Cov.: 28 AF XY: 0.0647 AC XY: 4796 AN XY: 74178

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0380

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0496

Gnomad4 FIN AF: 0.0935

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.0510

Alfa AF: 0.0243 Hom.: 17

Bravo AF: 0.0641

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs5743905; hg19: chr11-1322713;