chr19-4818366-T-C

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.12A>G(p.Thr4Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 1,599,354 control chromosomes in the GnomAD database, including 341,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T4T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.72 ( 40613 hom., cov: 33)

Exomes 𝑓: 0.64 ( 301105 hom. )

Consequence

TICAM1
NM_182919.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -4.35

Publications

27 publications found

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 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

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=-0.92).

BP6

Variant 19-4818366-T-C is Benign according to our data. Variant chr19-4818366-T-C is described in ClinVar as Benign. ClinVar VariationId is 403542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TICAM1	NM_182919.4	MANE Select	c.12A>G	p.Thr4Thr	synonymous	Exon 2 of 2	NP_891549.1
TICAM1	NM_001385678.1		c.5-35A>G		intron	N/A	NP_001372607.1
TICAM1	NM_001385679.1		c.-89-35A>G		intron	N/A	NP_001372608.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICAM1	ENST00000248244.6	TSL:1 MANE Select	c.12A>G	p.Thr4Thr	synonymous	Exon 2 of 2	ENSP00000248244.4

Frequencies

GnomAD3 genomes

AF:

0.718

AC:

109257

AN:

152068

Hom.:

40560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.700

Gnomad FIN

AF:

0.663

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.703

GnomAD2 exomes

AF:

0.658

AC:

154814

AN:

235140

AF XY:

0.656

show subpopulations

Gnomad AFR exome

AF:

0.928

Gnomad AMR exome

AF:

0.657

Gnomad ASJ exome

AF:

0.660

Gnomad EAS exome

AF:

0.569

Gnomad FIN exome

AF:

0.649

Gnomad NFE exome

AF:

0.626

Gnomad OTH exome

AF:

0.658

GnomAD4 exome

AF:

0.642

AC:

929502

AN:

1447168

Hom.:

301105

Cov.:

AF XY:

0.643

AC XY:

462095

AN XY:

719048

show subpopulations

African (AFR)

AF:

0.936

AC:

31022

AN:

33140

American (AMR)

AF:

0.662

AC:

28451

AN:

42962

Ashkenazi Jewish (ASJ)

AF:

0.664

AC:

16607

AN:

25004

East Asian (EAS)

AF:

0.624

AC:

24680

AN:

39582

South Asian (SAS)

AF:

0.698

AC:

58903

AN:

84440

European-Finnish (FIN)

AF:

0.648

AC:

33567

AN:

51788

Middle Eastern (MID)

AF:

0.702

AC:

3988

AN:

5680

European-Non Finnish (NFE)

AF:

0.627

AC:

693205

AN:

1104818

Other (OTH)

AF:

0.654

AC:

39079

AN:

59754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

20009

40017

60026

80034

100043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18706

37412

56118

74824

93530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.719

AC:

109367

AN:

152186

Hom.:

40613

Cov.:

AF XY:

0.719

AC XY:

53497

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.924

AC:

38406

AN:

41554

American (AMR)

AF:

0.684

AC:

10449

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.639

AC:

2217

AN:

3468

East Asian (EAS)

AF:

0.592

AC:

3057

AN:

5160

South Asian (SAS)

AF:

0.699

AC:

3372

AN:

4826

European-Finnish (FIN)

AF:

0.663

AC:

7019

AN:

10592

Middle Eastern (MID)

AF:

0.697

AC:

205

AN:

294

European-Non Finnish (NFE)

AF:

0.628

AC:

42716

AN:

67990

Other (OTH)

AF:

0.701

AC:

1480

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1517

3035

4552

6070

7587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.656

Hom.:

134527

Bravo

AF:

0.726

Asia WGS

AF:

0.649

AC:

2256

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

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 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported.

not provided

Benign:1Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.037

(source)

DANN

Benign

0.26

PhyloP100

-4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over