rs11466722

Variant names:

• chr19-4817276-AAGGAGGAGGAGG-A
• rs11466722
• NM_182919.4:c.1090_1101delCCTCCTCCTCCT

Your query was ambiguous. Multiple possible variants found:

• chr19-4817276-AAGGAGGAGGAGG-A
• chr19-4817276-AAGGAGGAGGAGG-AAGG
• chr19-4817276-AAGGAGGAGGAGG-AAGGAGG
• chr19-4817276-AAGGAGGAGGAGG-AAGGAGGAGG
• chr19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGAGGAGG
• chr19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGAGGAGGAGG
• chr19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGAGGAGGAGGAGG
• chr19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGAGGAGGAGGAGGAGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_182919.4(TICAM1):​c.1090_1101delCCTCCTCCTCCT​(p.Pro364_Pro367del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,580 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TICAM1 NM_182919.4 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.993
• Publications: 3 publications found

Genes affected

TICAM1 (HGNC:18348): (TIR domain containing adaptor molecule 1) This gene encodes an adaptor protein containing a Toll/interleukin-1 receptor (TIR) homology domain, which is an intracellular signaling domain that mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. This protein is involved in native immunity against invading pathogens. It specifically interacts with toll-like receptor 3, but not with other TLRs, and this association mediates dsRNA induction of interferon-beta through activation of nuclear factor kappa-B, during an antiviral immune response. Mutations in this gene are associated with encephalopathy, acute, infection-induced. [provided by RefSeq, Jul 2020]

TICAM1 Gene-Disease associations (from GenCC):

• herpes simplex encephalitis, susceptibility to, 4

  Inheritance: AR, AD, SD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182919.4. 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
	TICAM1	NM_182919.4	MANE Select	c.1090_1101delCCTCCTCCTCCT	p.Pro364_Pro367del	conservative_inframe_deletion	Exon 2 of 2	NP_891549.1	Q8IUC6
	TICAM1	NM_001385678.1		c.1048_1059delCCTCCTCCTCCT	p.Pro350_Pro353del	conservative_inframe_deletion	Exon 3 of 3	NP_001372607.1
	TICAM1	NM_001385679.1		c.955_966delCCTCCTCCTCCT	p.Pro319_Pro322del	conservative_inframe_deletion	Exon 2 of 2	NP_001372608.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICAM1	ENST00000248244.6	TSL:1 MANE Select	c.1090_1101delCCTCCTCCTCCT	p.Pro364_Pro367del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000248244.4	Q8IUC6
	TICAM1	ENST00000868535.1		c.1090_1101delCCTCCTCCTCCT	p.Pro364_Pro367del	conservative_inframe_deletion	Exon 3 of 3	ENSP00000538594.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455580 Hom.: 0 AF XY: 0.00000138 AC XY: 1 AN XY: 724162

African (AFR) AF: 0.00 AC: 0 AN: 33038

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107268

Other (OTH) AF: 0.00 AC: 0 AN: 60102

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.99

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11466722; hg19: chr19-4817288;