rs7255265

Variant names:

• chr19-4818366-T-C
• rs7255265
• NM_182919.4:c.12A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-4818366-T-C
• chr19-4818366-T-G
• chr19-4818366-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -4.35
• Publications: 27 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 -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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICAM1	NM_182919.4	MANE Select	c.12A>G	p.Thr4Thr	synonymous	Exon 2 of 2	NP_891549.1	Q8IUC6
	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

Sel.	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	Q8IUC6
	TICAM1	ENST00000868535.1		c.12A>G	p.Thr4Thr	synonymous	Exon 3 of 3	ENSP00000538594.1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109257 AN: 152068 Hom.: 40560 Cov.: 33

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

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.: 63 AF XY: 0.643 AC XY: 462095 AN XY: 719048

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

GnomAD4 genome AF: 0.719 AC: 109367 AN: 152186 Hom.: 40613 Cov.: 33 AF XY: 0.719 AC XY: 53497 AN XY: 74386

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

Alfa AF: 0.656 Hom.: 134527

Bravo AF: 0.726

Asia WGS AF: 0.649 AC: 2256 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Herpes simplex encephalitis, susceptibility to, 4 (1)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.037
DANN	Benign	0.26
PhyloP100		-4.3
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: rs7255265; hg19: chr19-4818378; COSMIC: COSV50232725; COSMIC: COSV50232725;