19-4816148-A-C

Variant names:

• chr19-4816148-A-C
• rs8120
• NM_182919.4:c.*91T>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182919.4(TICAM1):​c.*91T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,388,318 control chromosomes in the GnomAD database, including 45,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5701 hom., cov: 32)
  • Exomes 𝑓: 0.25 (40286 hom.)
• Consequence: TICAM1 NM_182919.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.648

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 19-4816148-A-C is Benign according to our data. Variant chr19-4816148-A-C is described in ClinVar as [Benign]. Clinvar id is 2688085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TICAM1	NM_182919.4	c.*91T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000248244.6	NP_891549.1
TICAM1	NM_001385678.1	c.*91T>G		3_prime_UTR_variant	Exon 3 of 3		NP_001372607.1
TICAM1	NM_001385679.1	c.*91T>G		3_prime_UTR_variant	Exon 2 of 2		NP_001372608.1
TICAM1	NM_001385680.1	c.*91T>G		3_prime_UTR_variant	Exon 3 of 3		NP_001372609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TICAM1	ENST00000248244	c.*91T>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_182919.4	ENSP00000248244.4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40463 AN: 151916 Hom.: 5693 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.251 AC: 310519 AN: 1236284 Hom.: 40286 Cov.: 30 AF XY: 0.250 AC XY: 149533 AN XY: 597454

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.266 AC: 40505 AN: 152034 Hom.: 5701 Cov.: 32 AF XY: 0.273 AC XY: 20317 AN XY: 74306

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.262

Alfa AF: 0.236 Hom.: 5528

Bravo AF: 0.261

Asia WGS AF: 0.333 AC: 1159 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

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 56% of patients studied by a panel of primary immunodeficiencies. Number of patients: 53. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.78
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs8120; hg19: chr19-4816160;