4-38804398-A-G

Variant names:

• chr4-38804398-A-G
• rs5743563
• ENST00000502213.7:c.-252T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000502213.7(TLR1):​c.-252T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,290 control chromosomes in the GnomAD database, including 2,243 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 (2242 hom., cov: 33)
  • Exomes 𝑓: 0.19 (1 hom.)
• Consequence: TLR1 ENST00000502213.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 31 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]

ENSG00000306984 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502213.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	NM_003263.4	MANE Select	c.-236-16T>C		intron	N/A	NP_003254.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000502213.7	TSL:1	c.-252T>C		5_prime_UTR	Exon 2 of 4	ENSP00000421259.1
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.-236-16T>C		intron	N/A	ENSP00000354932.2
	TLR1	ENST00000505940.1	TSL:3	c.-68+356T>C		intron	N/A	ENSP00000421856.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22240 AN: 152146 Hom.: 2242 Cov.: 33

Gnomad AFR AF: 0.0343

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.192 AC: 5 AN: 26 Hom.: 1 Cov.: 0 AF XY: 0.188 AC XY: 3 AN XY: 16

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.208 AC: 5 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.146 AC: 22233 AN: 152264 Hom.: 2242 Cov.: 33 AF XY: 0.145 AC XY: 10783 AN XY: 74444

African (AFR) AF: 0.0342 AC: 1421 AN: 41570

American (AMR) AF: 0.174 AC: 2669 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2079 AN: 5170

South Asian (SAS) AF: 0.196 AC: 946 AN: 4824

European-Finnish (FIN) AF: 0.0834 AC: 885 AN: 10610

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12389 AN: 68004

Other (OTH) AF: 0.202 AC: 426 AN: 2112

Alfa AF: 0.159 Hom.: 1441

Bravo AF: 0.152

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.42
PhyloP100		-0.51
PromoterAI		-0.040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: -16

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

Other links and lift over

dbSNP: rs5743563; hg19: chr4-38806019;