NM_003263.4:c.-160+536G>A

Variant names:

• chr4-38803770-C-T
• rs5743572
• NM_003263.4:c.-160+536G>A

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+536G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,190 control chromosomes in the GnomAD database, including 320 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 0.056 (320 hom., cov: 32)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4	c.-160+536G>A		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+536G>A		intron_variant	Intron 2 of 3	1	NM_003263.4	ENSP00000354932.2

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8502 AN: 152074 Hom.: 322 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0559 AC: 8509 AN: 152190 Hom.: 320 Cov.: 32 AF XY: 0.0553 AC XY: 4114 AN XY: 74426

African (AFR) AF: 0.101 AC: 4179 AN: 41488

American (AMR) AF: 0.0408 AC: 624 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3468

East Asian (EAS) AF: 0.0682 AC: 353 AN: 5176

South Asian (SAS) AF: 0.0707 AC: 341 AN: 4824

European-Finnish (FIN) AF: 0.0224 AC: 238 AN: 10608

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0352 AC: 2391 AN: 68004

Other (OTH) AF: 0.0728 AC: 154 AN: 2116

Alfa AF: 0.0446 Hom.: 155

Bravo AF: 0.0587

Asia WGS AF: 0.0890 AC: 309 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-0.82
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: rs5743572; hg19: chr4-38805391;