19-4817276-AAGGAGGAGGAGG-AAGGAGG

Variant names:

• chr19-4817276-AAGGAGG-A
• rs11466722
• NM_182919.4:c.1096_1101delCCTCCT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_182919.4(TICAM1):​c.1096_1101delCCTCCT​(p.Pro366_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 0.000163 in 1,603,258 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: TICAM1 NM_182919.4 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 19-4817276-AAGGAGG-A is Benign according to our data. Variant chr19-4817276-AAGGAGG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 712940.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1096_1101delCCTCCT	p.Pro366_Pro367del	conservative_inframe_deletion	Exon 2 of 2	NP_891549.1	Q8IUC6
	TICAM1	NM_001385678.1		c.1054_1059delCCTCCT	p.Pro352_Pro353del	conservative_inframe_deletion	Exon 3 of 3	NP_001372607.1
	TICAM1	NM_001385679.1		c.961_966delCCTCCT	p.Pro321_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.1096_1101delCCTCCT	p.Pro366_Pro367del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000248244.4	Q8IUC6
	TICAM1	ENST00000868535.1		c.1096_1101delCCTCCT	p.Pro366_Pro367del	conservative_inframe_deletion	Exon 3 of 3	ENSP00000538594.1

Frequencies

GnomAD3 genomes AF: 0.000129 AC: 19 AN: 147568 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000337

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000987

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000744

Gnomad OTH AF: 0.000493

GnomAD2 exomes AF: 0.000296 AC: 73 AN: 246324 AF XY: 0.000217

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000765

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000539

Gnomad OTH exome AF: 0.000500

GnomAD4 exome AF: 0.000167 AC: 243 AN: 1455572 Hom.: 1 AF XY: 0.000149 AC XY: 108 AN XY: 724160

African (AFR) AF: 0.000515 AC: 17 AN: 33038

American (AMR) AF: 0.00108 AC: 48 AN: 44626

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

East Asian (EAS) AF: 0.00113 AC: 45 AN: 39650

South Asian (SAS) AF: 0.0000698 AC: 6 AN: 85964

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

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5674

European-Non Finnish (NFE) AF: 0.0000849 AC: 94 AN: 1107262

Other (OTH) AF: 0.000532 AC: 32 AN: 60102

GnomAD4 genome AF: 0.000129 AC: 19 AN: 147686 Hom.: 0 Cov.: 27 AF XY: 0.000125 AC XY: 9 AN XY: 72068

African (AFR) AF: 0.0000513 AC: 2 AN: 38964

American (AMR) AF: 0.000337 AC: 5 AN: 14842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.000989 AC: 5 AN: 5056

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10266

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

European-Non Finnish (NFE) AF: 0.0000744 AC: 5 AN: 67206

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

Alfa AF: 0.0000840 Hom.: 133

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Herpes simplex encephalitis, susceptibility to, 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.99
Mutation Taster		=180/20	polymorphism

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;