19-4817276-AAGGAGGAGGAGG-AAGGAGGAGG

Variant names:

• chr19-4817276-AAGG-A
• rs11466722
• NM_182919.4:c.1099_1101delCCT

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_182919.4(TICAM1):​c.1099_1101delCCT​(p.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 0.000543 in 1,595,244 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 27)
  • Exomes 𝑓: 0.00043 (1 hom.)
• Consequence: TICAM1 NM_182919.4 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0450
• 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: Benign. The variant received -12 ACMG points.

• BP6: Variant 19-4817276-AAGG-A is Benign according to our data. Variant chr19-4817276-AAGG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 780505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR,SD,AD gene

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.1099_1101delCCT	p.Pro367del	conservative_inframe_deletion	Exon 2 of 2	NP_891549.1	Q8IUC6
	TICAM1	NM_001385678.1		c.1057_1059delCCT	p.Pro353del	conservative_inframe_deletion	Exon 3 of 3	NP_001372607.1
	TICAM1	NM_001385679.1		c.964_966delCCT	p.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.1099_1101delCCT	p.Pro367del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000248244.4	Q8IUC6
	TICAM1	ENST00000868535.1		c.1099_1101delCCT	p.Pro367del	conservative_inframe_deletion	Exon 3 of 3	ENSP00000538594.1

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 240 AN: 147542 Hom.: 2 Cov.: 27

Gnomad AFR AF: 0.00538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000472

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.000428

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000223

Gnomad OTH AF: 0.000493

GnomAD2 exomes AF: 0.000694 AC: 171 AN: 246324 AF XY: 0.000532

Gnomad AFR exome AF: 0.00516

Gnomad AMR exome AF: 0.00105

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.000437

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.000162

Gnomad OTH exome AF: 0.000500

GnomAD4 exome AF: 0.000432 AC: 626 AN: 1447584 Hom.: 1 AF XY: 0.000416 AC XY: 300 AN XY: 720348

African (AFR) AF: 0.00605 AC: 199 AN: 32906

American (AMR) AF: 0.00117 AC: 52 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25848

East Asian (EAS) AF: 0.000911 AC: 36 AN: 39538

South Asian (SAS) AF: 0.000805 AC: 69 AN: 85682

European-Finnish (FIN) AF: 0.0000754 AC: 4 AN: 53070

Middle Eastern (MID) AF: 0.00141 AC: 8 AN: 5662

European-Non Finnish (NFE) AF: 0.000188 AC: 207 AN: 1100558

Other (OTH) AF: 0.000836 AC: 50 AN: 59818

GnomAD4 genome AF: 0.00163 AC: 240 AN: 147660 Hom.: 2 Cov.: 27 AF XY: 0.00136 AC XY: 98 AN XY: 72054

African (AFR) AF: 0.00536 AC: 209 AN: 38958

American (AMR) AF: 0.000472 AC: 7 AN: 14840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00119 AC: 6 AN: 5056

South Asian (SAS) AF: 0.000429 AC: 2 AN: 4666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000223 AC: 15 AN: 67196

Other (OTH) AF: 0.000487 AC: 1 AN: 2052

Alfa AF: 0.000672 Hom.: 133

Bravo AF: 0.00192

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Herpes simplex encephalitis, susceptibility to, 4 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.045
Mutation Taster		=93/7	polymorphism

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: rs11466722; hg19: chr19-4817288; COSMIC: COSV50234544;