rs6510827

Positions:

• chr19-4830616-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182919.4(TICAM1):​c.-140+998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,082 control chromosomes in the GnomAD database, including 33,663 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 0.66 (33663 hom., cov: 33)
• Consequence: TICAM1 NM_182919.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TICAM1	NM_182919.4	c.-140+998A>G		intron_variant		ENST00000248244.6	NP_891549.1
TICAM1	NM_001385678.1	c.-39+998A>G		intron_variant			NP_001372607.1
TICAM1	NM_001385679.1	c.-90+998A>G		intron_variant			NP_001372608.1
TICAM1	NM_001385680.1	c.-205+998A>G		intron_variant			NP_001372609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TICAM1	ENST00000248244.6	c.-140+998A>G		intron_variant		1	NM_182919.4	ENSP00000248244.4

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100271 AN: 151964 Hom.: 33623 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.660 AC: 100371 AN: 152082 Hom.: 33663 Cov.: 33 AF XY: 0.661 AC XY: 49133 AN XY: 74334

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.644

Alfa AF: 0.615 Hom.: 60181

Bravo AF: 0.662

Asia WGS AF: 0.644 AC: 2240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.087
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6510827; hg19: chr19-4830628;