chr11-1301483-G-C

Variant names:

• chr11-1301483-G-C
• rs5743905
• NM_019009.4:c.34-5689C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TOLLIP	NM_019009.4	c.34-5689C>G		intron_variant	Intron 1 of 5	ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.34-5689C>G		intron_variant	Intron 1 of 5	1	NM_019009.4	ENSP00000314733.5

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

African (AFR) AF: 0.0617 AC: 2551 AN: 41348

American (AMR) AF: 0.110 AC: 1675 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 132 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5158

South Asian (SAS) AF: 0.0496 AC: 237 AN: 4782

European-Finnish (FIN) AF: 0.0935 AC: 985 AN: 10532

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3602 AN: 67970

Other (OTH) AF: 0.0510 AC: 107 AN: 2100

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
PhyloP100		0.097
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5743905; hg19: chr11-1322713;