Variant chr19-4816229-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.340

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 -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TICAM1	ENST00000248244.6 linkuse as main transcript	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.149

AC XY:

98386

AN XY:

660318

show subpopulations

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.:

AF XY:

0.174

AC XY:

12941

AN XY:

74390

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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