4-38801634-A-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003263.4(TLR1):​c.-159-686T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,104 control chromosomes in the GnomAD database, including 6,997 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 0.28 (6997 hom., cov: 32)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43256 AN: 151986 Hom.: 6991 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.285 AC: 43294 AN: 152104 Hom.: 6997 Cov.: 32 AF XY: 0.287 AC XY: 21317 AN XY: 74388

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.333

Alfa AF: 0.0788 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	0.84
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs4540055; hg19: chr4-38803255;