rs4807000

Variant names:

• chr19-4831866-A-G
• rs4807000
• NM_182919.4:c.-392T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-4831866-A-G
• chr19-4831866-A-T

Variant summary

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

The NM_182919.4(TICAM1):​c.-392T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,838 control chromosomes in the GnomAD database, including 34,446 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 0.67 (34446 hom., cov: 31)
• Consequence: TICAM1 NM_182919.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TICAM1	NM_182919.4	c.-392T>C		upstream_gene_variant		ENST00000248244.6	NP_891549.1
TICAM1	NM_001385678.1	c.-291T>C		upstream_gene_variant			NP_001372607.1
TICAM1	NM_001385679.1	c.-342T>C		upstream_gene_variant			NP_001372608.1
TICAM1	NM_001385680.1	c.-457T>C		upstream_gene_variant			NP_001372609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TICAM1	ENST00000248244.6	c.-392T>C		upstream_gene_variant		1	NM_182919.4	ENSP00000248244.4

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101250 AN: 151720 Hom.: 34406 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.667 AC: 101350 AN: 151838 Hom.: 34446 Cov.: 31 AF XY: 0.669 AC XY: 49614 AN XY: 74210

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.650

Alfa AF: 0.633 Hom.: 3860

Bravo AF: 0.669

Asia WGS AF: 0.645 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4807000; hg19: chr19-4831878;