19-4816229-G-A

Variant names:

• chr19-4816229-G-A
• rs1046673
• NM_182919.4:c.*10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182919.4(TICAM1):​c.*10C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,502,008 control chromosomes in the GnomAD database, including 18,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2784 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15826 hom.)
• Consequence: TICAM1 NM_182919.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.340
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-4816229-G-A is Benign according to our data. Variant chr19-4816229-G-A is described in ClinVar as Benign. ClinVar VariationId is 403539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

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.*10C>T		3_prime_UTR	Exon 2 of 2	NP_891549.1	Q8IUC6
	TICAM1	NM_001385678.1		c.*10C>T		3_prime_UTR	Exon 3 of 3	NP_001372607.1
	TICAM1	NM_001385679.1		c.*10C>T		3_prime_UTR	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.*10C>T		3_prime_UTR	Exon 2 of 2	ENSP00000248244.4	Q8IUC6
	TICAM1	ENST00000868535.1		c.*10C>T		3_prime_UTR	Exon 3 of 3	ENSP00000538594.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27128 AN: 152050 Hom.: 2789 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.144 AC: 24574 AN: 171030 AF XY: 0.143

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.0986

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.0850

Gnomad FIN exome AF: 0.0730

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.149 AC: 201146 AN: 1349840 Hom.: 15826 Cov.: 36 AF XY: 0.149 AC XY: 98386 AN XY: 660318

African (AFR) AF: 0.297 AC: 8892 AN: 29988

American (AMR) AF: 0.104 AC: 2928 AN: 28186

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 3461 AN: 19716

East Asian (EAS) AF: 0.0796 AC: 3057 AN: 38386

South Asian (SAS) AF: 0.135 AC: 9360 AN: 69144

European-Finnish (FIN) AF: 0.0791 AC: 3407 AN: 43062

Middle Eastern (MID) AF: 0.208 AC: 915 AN: 4398

European-Non Finnish (NFE) AF: 0.151 AC: 160434 AN: 1061344

Other (OTH) AF: 0.156 AC: 8692 AN: 55616

GnomAD4 genome AF: 0.178 AC: 27140 AN: 152168 Hom.: 2784 Cov.: 32 AF XY: 0.174 AC XY: 12941 AN XY: 74390

African (AFR) AF: 0.287 AC: 11890 AN: 41500

American (AMR) AF: 0.136 AC: 2076 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3472

East Asian (EAS) AF: 0.0816 AC: 422 AN: 5172

South Asian (SAS) AF: 0.132 AC: 636 AN: 4816

European-Finnish (FIN) AF: 0.0714 AC: 759 AN: 10626

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.150 AC: 10187 AN: 68002

Other (OTH) AF: 0.186 AC: 392 AN: 2110

Alfa AF: 0.163 Hom.: 1562

Bravo AF: 0.191

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.58
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs1046673; hg19: chr19-4816241; COSMIC: COSV50235336; COSMIC: COSV50235336;