chr19-4818366-T-C

Position:

chr19-4818366-T-C

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 made for transcript

Verdict is Benign. Variant got -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 id is 403542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-4818366-T-C is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TICAM1	NM_182919.4 linkuse as main transcript	c.12A>G	p.Thr4Thr	synonymous_variant	2/2	ENST00000248244.6	NP_891549.1	Q8IUC6
TICAM1	NM_001385678.1 linkuse as main transcript	c.5-35A>G		intron_variant			NP_001372607.1
TICAM1	NM_001385679.1 linkuse as main transcript	c.-89-35A>G		intron_variant			NP_001372608.1
TICAM1	NM_001385680.1 linkuse as main transcript	c.-72+18A>G		intron_variant			NP_001372609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TICAM1	ENST00000248244.6 linkuse as main transcript	c.12A>G	p.Thr4Thr	synonymous_variant	2/2	1	NM_182919.4	ENSP00000248244.4		Q8IUC6

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

GnomAD3 exomes

AF:

0.658

AC:

154814

AN:

235140

Hom.:

51545

AF XY:

0.656

AC XY:

84143

AN XY:

128206

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 SAS exome

AF:

0.697

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

Gnomad4 AFR exome

AF:

0.936

Gnomad4 AMR exome

AF:

0.662

Gnomad4 ASJ exome

AF:

0.664

Gnomad4 EAS exome

AF:

0.624

Gnomad4 SAS exome

AF:

0.698

Gnomad4 FIN exome

AF:

0.648

Gnomad4 NFE exome

AF:

0.627

Gnomad4 OTH exome

AF:

0.654

GnomAD4 genome

AF:

0.719

AC:

109367

AN:

152186

Hom.:

40613

Cov.:

AF XY:

0.719

AC XY:

53497

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.924

Gnomad4 AMR

AF:

0.684

Gnomad4 ASJ

AF:

0.639

Gnomad4 EAS

AF:

0.592

Gnomad4 SAS

AF:

0.699

Gnomad4 FIN

AF:

0.663

Gnomad4 NFE

AF:

0.628

Gnomad4 OTH

AF:

0.701

Alfa

AF:

0.642

Hom.:

56072

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

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 -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	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

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Herpes simplex encephalitis, susceptibility to, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.037

DANN

Benign

0.26

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. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over