19-4816148-A-C

Position:

• chr19-4816148-A-C

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/exons	MANE	UniProt
TICAM1	NM_182919.4	c.*91T>G		3_prime_UTR_variant	2/2	ENST00000248244.6
TICAM1	NM_001385678.1	c.*91T>G		3_prime_UTR_variant	3/3
TICAM1	NM_001385679.1	c.*91T>G		3_prime_UTR_variant	2/2
TICAM1	NM_001385680.1	c.*91T>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TICAM1	ENST00000248244.6	c.*91T>G		3_prime_UTR_variant	2/2	1	NM_182919.4	P1

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

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 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;