4-38809930-G-A

Variant names:

• chr4-38809930-G-A
• rs2101521
• ENST00000506146.5:c.-352-4737C>T

Variant summary

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

The ENST00000506146.5(TLR1):​c.-352-4737C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,092 control chromosomes in the GnomAD database, including 12,214 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 0.36 (12214 hom., cov: 33)
• Consequence: TLR1 ENST00000506146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 47 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000506146.5	c.-352-4737C>T		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54749 AN: 151974 Hom.: 12179 Cov.: 33

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.361 AC: 54843 AN: 152092 Hom.: 12214 Cov.: 33 AF XY: 0.361 AC XY: 26838 AN XY: 74360

African (AFR) AF: 0.587 AC: 24327 AN: 41446

American (AMR) AF: 0.449 AC: 6870 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1391 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3035 AN: 5186

South Asian (SAS) AF: 0.370 AC: 1783 AN: 4818

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10576

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14971 AN: 67992

Other (OTH) AF: 0.414 AC: 875 AN: 2114

Alfa AF: 0.286 Hom.: 12907

Bravo AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.66
DANN	Benign	0.75
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs2101521; hg19: chr4-38811551;