rs4963060

Variant names:

• chr11-1299830-G-A
• rs4963060
• NM_019009.4:c.34-4036C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1299830-G-A
• chr11-1299830-G-C

Variant summary

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

The NM_019009.4(TOLLIP):​c.34-4036C>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 NM_019009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019009.4. 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
	TOLLIP	NM_019009.4	MANE Select	c.34-4036C>T		intron	N/A	NP_061882.2
	TOLLIP	NM_001318512.2		c.34-9421C>T		intron	N/A	NP_001305441.1
	TOLLIP	NM_001318516.2		c.34-4036C>T		intron	N/A	NP_001305445.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP	ENST00000317204.11	TSL:1 MANE Select	c.34-4036C>T		intron	N/A	ENSP00000314733.5
	TOLLIP	ENST00000263646.11	TSL:5	c.13-4099C>T		intron	N/A	ENSP00000263646.6
	TOLLIP	ENST00000525159.5	TSL:2	c.34-4036C>T		intron	N/A	ENSP00000432668.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37565 AN: 152020 Hom.: 5008 Cov.: 33

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

African (AFR) AF: 0.193 AC: 8028 AN: 41504

American (AMR) AF: 0.203 AC: 3108 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1036 AN: 3466

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5170

South Asian (SAS) AF: 0.231 AC: 1116 AN: 4824

European-Finnish (FIN) AF: 0.198 AC: 2101 AN: 10588

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21223 AN: 67974

Other (OTH) AF: 0.251 AC: 531 AN: 2114

Alfa AF: 0.234 Hom.: 972

Bravo AF: 0.244

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.94
PhyloP100		-0.62
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: rs4963060; hg19: chr11-1321060;