4-38804475-T-C

Position:

• chr4-38804475-T-C

Variant summary

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

The NM_003263.4(TLR1):​c.-236-93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,246 control chromosomes in the GnomAD database, including 2,244 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 0.15 (2244 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	NM_003263.4	c.-236-93A>G		intron_variant		ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7	c.-236-93A>G		intron_variant		1	NM_003263.4	ENSP00000354932	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22248 AN: 152128 Hom.: 2244 Cov.: 33

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0840

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.204

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.146 AC: 22241 AN: 152246 Hom.: 2244 Cov.: 33 AF XY: 0.145 AC XY: 10792 AN XY: 74448

Gnomad4 AFR AF: 0.0343

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0840

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.201

Alfa AF: 0.163 Hom.: 560

Bravo AF: 0.152

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.4
DANN	Benign	0.80

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: rs5743562; hg19: chr4-38806096;