rs2292151

Variant names:

• chr19-4816707-G-A
• rs2292151
• NM_182919.4:c.1671C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182919.4(TICAM1):​c.1671C>T​(p.Asp557Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,613,854 control chromosomes in the GnomAD database, including 53,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4939 hom., cov: 33)
  • Exomes 𝑓: 0.25 (48088 hom.)
• Consequence: TICAM1 NM_182919.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.386
• Publications: 27 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-4816707-G-A is Benign according to our data. Variant chr19-4816707-G-A is described in ClinVar as Benign. ClinVar VariationId is 403540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.386 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 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.1671C>T	p.Asp557Asp	synonymous	Exon 2 of 2	NP_891549.1	Q8IUC6
	TICAM1	NM_001385678.1		c.1629C>T	p.Asp543Asp	synonymous	Exon 3 of 3	NP_001372607.1
	TICAM1	NM_001385679.1		c.1536C>T	p.Asp512Asp	synonymous	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.1671C>T	p.Asp557Asp	synonymous	Exon 2 of 2	ENSP00000248244.4	Q8IUC6
	TICAM1	ENST00000868535.1		c.1671C>T	p.Asp557Asp	synonymous	Exon 3 of 3	ENSP00000538594.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36781 AN: 152070 Hom.: 4935 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.243

GnomAD2 exomes AF: 0.274 AC: 68834 AN: 251030 AF XY: 0.272

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.341

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.414

Gnomad FIN exome AF: 0.360

Gnomad NFE exome AF: 0.238

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.252 AC: 368104 AN: 1461666 Hom.: 48088 Cov.: 82 AF XY: 0.251 AC XY: 182755 AN XY: 727134

African (AFR) AF: 0.166 AC: 5565 AN: 33480

American (AMR) AF: 0.340 AC: 15206 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6318 AN: 26132

East Asian (EAS) AF: 0.458 AC: 18189 AN: 39700

South Asian (SAS) AF: 0.259 AC: 22318 AN: 86258

European-Finnish (FIN) AF: 0.355 AC: 18880 AN: 53234

Middle Eastern (MID) AF: 0.216 AC: 1246 AN: 5762

European-Non Finnish (NFE) AF: 0.239 AC: 265282 AN: 1111998

Other (OTH) AF: 0.250 AC: 15100 AN: 60392

GnomAD4 genome AF: 0.242 AC: 36801 AN: 152188 Hom.: 4939 Cov.: 33 AF XY: 0.249 AC XY: 18559 AN XY: 74396

African (AFR) AF: 0.169 AC: 7026 AN: 41550

American (AMR) AF: 0.290 AC: 4433 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2175 AN: 5158

South Asian (SAS) AF: 0.269 AC: 1298 AN: 4828

European-Finnish (FIN) AF: 0.368 AC: 3895 AN: 10594

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16466 AN: 67984

Other (OTH) AF: 0.240 AC: 507 AN: 2112

Alfa AF: 0.242 Hom.: 19671

Bravo AF: 0.234

Asia WGS AF: 0.324 AC: 1127 AN: 3478

EpiCase AF: 0.232

EpiControl AF: 0.233

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.84
PhyloP100		-0.39
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: rs2292151; hg19: chr19-4816719; COSMIC: COSV50229420;