chr4-38801634-A-C

Variant names:

• chr4-38801634-A-C
• rs4540055
• NM_003263.4:c.-159-686T>G

Variant summary

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

The NM_003263.4(TLR1):​c.-159-686T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,130 control chromosomes in the GnomAD database, including 4,673 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 0.16 (4673 hom., cov: 32)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4	c.-159-686T>G		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.-159-686T>G		intron_variant	Intron 2 of 3	1	NM_003263.4	ENSP00000354932.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24290 AN: 152012 Hom.: 4652 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.0757

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.160 AC: 24364 AN: 152130 Hom.: 4673 Cov.: 32 AF XY: 0.157 AC XY: 11693 AN XY: 74396

African (AFR) AF: 0.460 AC: 19070 AN: 41472

American (AMR) AF: 0.0921 AC: 1408 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3470

East Asian (EAS) AF: 0.0753 AC: 389 AN: 5164

South Asian (SAS) AF: 0.176 AC: 848 AN: 4830

European-Finnish (FIN) AF: 0.0107 AC: 114 AN: 10606

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0278 AC: 1890 AN: 67978

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.00907 Hom.: 63

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
DANN	Benign	0.18
PhyloP100		-0.61
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: rs4540055; hg19: chr4-38803255;