rs11466722

chr19-4817276-AAGGAGGAGGAGG-Achr19-4817276-AAGGAGGAGGAGG-AAGGchr19-4817276-AAGGAGGAGGAGG-AAGGAGGchr19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGchr19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGAGGAGGchr19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGAGGAGGAGGchr19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGAGGAGGAGGAGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182919.4(TICAM1):c.1090_1101del(p.Pro364_Pro367del) variant causes a 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. 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 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.993

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TICAM1	NM_182919.4	c.1090_1101del	p.Pro364_Pro367del	inframe_deletion	2/2	ENST00000248244.6
TICAM1	NM_001385678.1	c.1048_1059del	p.Pro350_Pro353del	inframe_deletion	3/3
TICAM1	NM_001385679.1	c.955_966del	p.Pro319_Pro322del	inframe_deletion	2/2
TICAM1	NM_001385680.1	c.448_459del	p.Pro150_Pro153del	inframe_deletion	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TICAM1	ENST00000248244.6	c.1090_1101del	p.Pro364_Pro367del	inframe_deletion	2/2	1	NM_182919.4	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11466722; hg19: chr19-4817288;