4-38804362-T-C

Variant names:

• chr4-38804362-T-C
• rs5743565
• NM_003263.4:c.-216A>G

Variant summary

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

The NM_003263.4(TLR1):​c.-216A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,276 control chromosomes in the GnomAD database, including 2,250 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 (2245 hom., cov: 32)
  • Exomes 𝑓: 0.26 (5 hom.)
• Consequence: TLR1 NM_003263.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 33 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003263.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	NM_003263.4	MANE Select	c.-216A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	NP_003254.2
	TLR1	NM_003263.4	MANE Select	c.-216A>G		5_prime_UTR	Exon 2 of 4	NP_003254.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.-216A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000354932.2
	TLR1	ENST00000502213.7	TSL:1	c.-216A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000421259.1
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.-216A>G		5_prime_UTR	Exon 2 of 4	ENSP00000354932.2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22250 AN: 152096 Hom.: 2245 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.258 AC: 16 AN: 62 Hom.: 5 Cov.: 0 AF XY: 0.267 AC XY: 8 AN XY: 30

African (AFR) AC: 0 AN: 0

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: 0.267 AC: 16 AN: 60

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.146 AC: 22243 AN: 152214 Hom.: 2245 Cov.: 32 AF XY: 0.145 AC XY: 10789 AN XY: 74412

African (AFR) AF: 0.0343 AC: 1424 AN: 41556

American (AMR) AF: 0.175 AC: 2670 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2084 AN: 5164

South Asian (SAS) AF: 0.196 AC: 947 AN: 4830

European-Finnish (FIN) AF: 0.0837 AC: 887 AN: 10602

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

European-Non Finnish (NFE) AF: 0.182 AC: 12387 AN: 67978

Other (OTH) AF: 0.202 AC: 428 AN: 2116

Alfa AF: 0.144 Hom.: 1034

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	-0.81
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		0.56
PromoterAI		0.20	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5743565; hg19: chr4-38805983;