rs2292151

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.386

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id is 403540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-4816707-G-A is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TICAM1	NM_182919.4 link	c.1671C>T	p.Asp557Asp	synonymous_variant	Exon 2 of 2	ENST00000248244.6	NP_891549.1	Q8IUC6
TICAM1	NM_001385678.1 link	c.1629C>T	p.Asp543Asp	synonymous_variant	Exon 3 of 3		NP_001372607.1
TICAM1	NM_001385679.1 link	c.1536C>T	p.Asp512Asp	synonymous_variant	Exon 2 of 2		NP_001372608.1
TICAM1	NM_001385680.1 link	c.1029C>T	p.Asp343Asp	synonymous_variant	Exon 3 of 3		NP_001372609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TICAM1	ENST00000248244.6 link	c.1671C>T	p.Asp557Asp	synonymous_variant	Exon 2 of 2	1	NM_182919.4	ENSP00000248244.4		Q8IUC6

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36781

AN:

152070

Hom.:

4935

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.251

AC XY:

182755

AN XY:

727134

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

20407

40814

61220

81627

102034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.242

AC:

36801

AN:

152188

Hom.:

4939

Cov.:

AF XY:

0.249

AC XY:

18559

AN XY:

74396

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16466

AN:

67984

Other (OTH)

AF:

0.240

AC:

507

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1455

2910

4366

5821

7276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 62% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Herpes simplex encephalitis, susceptibility to, 4

Benign:1

Feb 03, 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

-0.81

CADD

Benign

4.0

(source)

DANN

Benign

0.84

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Below is the list of publications found by LitVar for variant 19:4816707 G>A . It may be empty.

rs2292151

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over