rs7873784

Variant names:

• chr9-117716658-G-C
• rs7873784
• NM_138554.5:c.*2010G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-117716658-G-C
• chr9-117716658-G-A
• chr9-117716658-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138554.5(TLR4):​c.*2010G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,100 control chromosomes in the GnomAD database, including 2,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2074 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLR4 NM_138554.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.719
• Publications: 95 publications found

Genes affected

TLR4 (HGNC:11850): (toll like receptor 4) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. In silico studies have found a particularly strong binding of surface TLR4 with the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease-2019 (COVID-19). This receptor has also been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness, and with susceptibility to age-related macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

TLR4 Gene-Disease associations (from GenCC):

• inflammatory bowel disease

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ENSG00000285082 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 9-117716658-G-C is Benign according to our data. Variant chr9-117716658-G-C is described in ClinVar as Benign. ClinVar VariationId is 1276780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138554.5. 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
	TLR4	NM_138554.5	MANE Select	c.*2010G>C		3_prime_UTR	Exon 3 of 3	NP_612564.1	O00206-1
	TLR4	NM_003266.4		c.*2010G>C		3_prime_UTR	Exon 4 of 4	NP_003257.1	O00206-2
	TLR4	NM_138557.3		c.*2010G>C		3_prime_UTR	Exon 2 of 2	NP_612567.1	O00206-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR4	ENST00000355622.8	TSL:1 MANE Select	c.*2010G>C		3_prime_UTR	Exon 3 of 3	ENSP00000363089.5	O00206-1
	ENSG00000285082	ENST00000697666.1		c.140+7929G>C		intron	N/A	ENSP00000513391.1	A0A8V8TMK6
	ENSG00000285082	ENST00000646089.2		c.93+12093G>C		intron	N/A	ENSP00000496197.1	A0A2R8YGN2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24422 AN: 151982 Hom.: 2065 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0908

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.151

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.161 AC: 24462 AN: 152100 Hom.: 2074 Cov.: 32 AF XY: 0.156 AC XY: 11626 AN XY: 74360

African (AFR) AF: 0.212 AC: 8778 AN: 41488

American (AMR) AF: 0.132 AC: 2012 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3466

East Asian (EAS) AF: 0.108 AC: 559 AN: 5176

South Asian (SAS) AF: 0.119 AC: 576 AN: 4830

European-Finnish (FIN) AF: 0.0908 AC: 960 AN: 10572

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10422 AN: 67974

Other (OTH) AF: 0.155 AC: 327 AN: 2110

Alfa AF: 0.0573 Hom.: 69

Bravo AF: 0.165

Asia WGS AF: 0.126 AC: 438 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.47
DANN	Benign	0.42
PhyloP100		-0.72
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: rs7873784; hg19: chr9-120478936;