rs5743604

Variant names:

• chr4-38799664-A-G
• rs5743604
• NM_003263.4:c.-67-766T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003263.4(TLR1):​c.-67-766T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,052 control chromosomes in the GnomAD database, including 12,054 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 0.36 (12054 hom., cov: 32)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• Publications: 36 publications found

Genes affected

TLR1 (HGNC:11847): (toll like receptor 1) 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 (PAMPs) 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. This gene is ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4	c.-67-766T>C		intron_variant	Intron 3 of 3	ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7	c.-67-766T>C		intron_variant	Intron 3 of 3	1	NM_003263.4	ENSP00000354932.2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54908 AN: 151934 Hom.: 12021 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.362 AC: 54997 AN: 152052 Hom.: 12054 Cov.: 32 AF XY: 0.363 AC XY: 26984 AN XY: 74328

African (AFR) AF: 0.566 AC: 23447 AN: 41454

American (AMR) AF: 0.472 AC: 7202 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3468

East Asian (EAS) AF: 0.528 AC: 2721 AN: 5154

South Asian (SAS) AF: 0.413 AC: 1993 AN: 4820

European-Finnish (FIN) AF: 0.110 AC: 1165 AN: 10612

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15759 AN: 67964

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.290 Hom.: 1015

Bravo AF: 0.397

Asia WGS AF: 0.464 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.050
DANN	Benign	0.41
PhyloP100		-2.8
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: rs5743604; hg19: chr4-38801285;