4-38819365-T-C

Variant names:

• chr4-38819365-T-C
• rs7696175
• ENST00000506146.5:c.-352-14172A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 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=-0.86).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000506146.5	c.-352-14172A>G		intron_variant	Intron 1 of 5	4		ENSP00000423725.1

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

African (AFR) AF: 0.918 AC: 38130 AN: 41532

American (AMR) AF: 0.646 AC: 9871 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2398 AN: 3472

East Asian (EAS) AF: 0.838 AC: 4325 AN: 5164

South Asian (SAS) AF: 0.726 AC: 3503 AN: 4828

European-Finnish (FIN) AF: 0.511 AC: 5396 AN: 10570

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.561 AC: 38133 AN: 67952

Other (OTH) AF: 0.707 AC: 1494 AN: 2112

Alfa AF: 0.606 Hom.: 57547

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
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs7696175; hg19: chr4-38820986;