4-38803574-A-G

Variant names:

• chr4-38803574-A-G
• rs5743574
• NM_003263.4:c.-160+732T>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.-160+732T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 152,138 control chromosomes in the GnomAD database, including 218 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 0.037 (218 hom., cov: 32)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 0 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]

ENSG00000306984 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4	c.-160+732T>C		intron_variant	Intron 2 of 3	ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7	c.-160+732T>C		intron_variant	Intron 2 of 3	1	NM_003263.4	ENSP00000354932.2

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5634 AN: 152020 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0682

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.00884

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00854

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0371 AC: 5639 AN: 152138 Hom.: 218 Cov.: 32 AF XY: 0.0370 AC XY: 2752 AN XY: 74404

African (AFR) AF: 0.0923 AC: 3815 AN: 41348

American (AMR) AF: 0.0196 AC: 300 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3472

East Asian (EAS) AF: 0.0680 AC: 353 AN: 5190

South Asian (SAS) AF: 0.0633 AC: 306 AN: 4834

European-Finnish (FIN) AF: 0.00884 AC: 94 AN: 10628

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00854 AC: 581 AN: 68038

Other (OTH) AF: 0.0445 AC: 94 AN: 2114

Alfa AF: 0.0451 Hom.: 102

Bravo AF: 0.0401

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		1.3
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: rs5743574; hg19: chr4-38805195;