4-38819365-T-C

Position:

• chr4-38819365-T-C

Variant summary

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

The ENST00000506146.5(TLR1):​c.-352-14172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,116 control chromosomes in the GnomAD database, including 37,623 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 0.68 (37623 hom., cov: 31)
• Consequence: TLR1 ENST00000506146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR1	ENST00000506146.5	c.-352-14172A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103837 AN: 151998 Hom.: 37555 Cov.: 31

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.683 AC: 103965 AN: 152116 Hom.: 37623 Cov.: 31 AF XY: 0.681 AC XY: 50655 AN XY: 74362

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.707

Alfa AF: 0.601 Hom.: 41202

Bravo AF: 0.703

Asia WGS AF: 0.788 AC: 2737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7696175; hg19: chr4-38820986;