19-4816229-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.340

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 403539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TICAM1	NM_182919.4	c.*10C>T		3_prime_UTR_variant	2/2	ENST00000248244.6
TICAM1	NM_001385678.1	c.*10C>T		3_prime_UTR_variant	3/3
TICAM1	NM_001385679.1	c.*10C>T		3_prime_UTR_variant	2/2
TICAM1	NM_001385680.1	c.*10C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TICAM1	ENST00000248244.6	c.*10C>T		3_prime_UTR_variant	2/2	1	NM_182919.4	P1

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

GnomAD3 exomes AF: 0.144 AC: 24574 AN: 171030 Hom.: 2031 AF XY: 0.143 AC XY: 12905 AN XY: 90298

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 SAS exome AF: 0.128

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

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.0796

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.0791

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.156

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

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0816

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0714

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.186

Alfa AF: 0.161 Hom.: 1027

Bravo AF: 0.191

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.3
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

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