19-4818072-C-T

Variant names:

• chr19-4818072-C-T
• rs11466720
• NM_182919.4:c.306G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_182919.4(TICAM1):​c.306G>A​(p.Leu102Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,607,704 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (1 hom.)
• Consequence: TICAM1 NM_182919.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.617
• Publications: 0 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, SD, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-4818072-C-T is Benign according to our data. Variant chr19-4818072-C-T is described in ClinVar as [Benign]. Clinvar id is 540520.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TICAM1	NM_182919.4	c.306G>A	p.Leu102Leu	synonymous_variant	Exon 2 of 2	ENST00000248244.6	NP_891549.1
TICAM1	NM_001385678.1	c.264G>A	p.Leu88Leu	synonymous_variant	Exon 3 of 3		NP_001372607.1
TICAM1	NM_001385679.1	c.171G>A	p.Leu57Leu	synonymous_variant	Exon 2 of 2		NP_001372608.1
TICAM1	NM_001385680.1	c.-71-266G>A		intron_variant	Intron 2 of 2		NP_001372609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TICAM1	ENST00000248244.6	c.306G>A	p.Leu102Leu	synonymous_variant	Exon 2 of 2	1	NM_182919.4	ENSP00000248244.4

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 191 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00429

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000312 AC: 76 AN: 243760 AF XY: 0.000219

Gnomad AFR exome AF: 0.00393

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.0000989 AC: 144 AN: 1455376 Hom.: 1 Cov.: 80 AF XY: 0.0000828 AC XY: 60 AN XY: 724294

African (AFR) AF: 0.00308 AC: 103 AN: 33474

American (AMR) AF: 0.000559 AC: 25 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111846

Other (OTH) AF: 0.000182 AC: 11 AN: 60328

GnomAD4 genome AF: 0.00125 AC: 191 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74484

African (AFR) AF: 0.00428 AC: 178 AN: 41572

American (AMR) AF: 0.000719 AC: 11 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00137

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

TICAM1-related disorder Benign:1

Dec 11, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Herpes simplex encephalitis, susceptibility to, 4 Benign:1

Jan 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.4
DANN	Benign	0.82
PhyloP100		0.62
Mutation Taster		=100/0	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: rs11466720; hg19: chr19-4818084;