19-4822843-A-G

Variant names:

• chr19-4822843-A-G
• rs4807651
• NM_182919.4:c.-139-4327T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182919.4(TICAM1):​c.-139-4327T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,024 control chromosomes in the GnomAD database, including 9,066 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9066 hom., cov: 32)
• Consequence: TICAM1 NM_182919.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 13 publications found

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, AD, SD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICAM1	NM_182919.4	MANE Select	c.-139-4327T>C		intron	N/A	NP_891549.1	Q8IUC6
	TICAM1	NM_001385678.1		c.-38-4327T>C		intron	N/A	NP_001372607.1
	TICAM1	NM_001385679.1		c.-89-4512T>C		intron	N/A	NP_001372608.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICAM1	ENST00000248244.6	TSL:1 MANE Select	c.-139-4327T>C		intron	N/A	ENSP00000248244.4	Q8IUC6
	TICAM1	ENST00000868535.1		c.-588-2996T>C		intron	N/A	ENSP00000538594.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50315 AN: 151906 Hom.: 9063 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50323 AN: 152024 Hom.: 9066 Cov.: 32 AF XY: 0.335 AC XY: 24894 AN XY: 74294

African (AFR) AF: 0.198 AC: 8222 AN: 41488

American (AMR) AF: 0.376 AC: 5723 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1083 AN: 3470

East Asian (EAS) AF: 0.466 AC: 2402 AN: 5160

South Asian (SAS) AF: 0.315 AC: 1520 AN: 4822

European-Finnish (FIN) AF: 0.452 AC: 4766 AN: 10554

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25552 AN: 67974

Other (OTH) AF: 0.333 AC: 704 AN: 2114

Alfa AF: 0.355 Hom.: 12680

Bravo AF: 0.321

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.39
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4807651; hg19: chr19-4822855;