dbSNP rs4624663: TLR1:c.*216A>G (chr4-38796255-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003263.4(TLR1):c.*216A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 546,750 control chromosomes in the GnomAD database, including 368 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 0.039 ( 165 hom., cov: 32)

Exomes 𝑓: 0.026 ( 203 hom. )

Consequence

TLR1
NM_003263.4 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.261

Publications

10 publications found

Variant links:

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]

TLR1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4 link	c.*216A>G		splice_region_variant	Exon 4 of 4	ENST00000308979.7	NP_003254.2
TLR1	NM_003263.4 link	c.*216A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000308979.7	NP_003254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7 link	c.*216A>G		splice_region_variant	Exon 4 of 4	1	NM_003263.4	ENSP00000354932.2
TLR1	ENST00000308979.7 link	c.*216A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_003263.4	ENSP00000354932.2

Frequencies

GnomAD3 genomes

AF:

0.0390

AC:

5942

AN:

152186

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0759

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0272

Gnomad OTH

AF:

0.0439

GnomAD4 exome

AF:

0.0262

AC:

10322

AN:

394446

Hom.:

203

Cov.:

AF XY:

0.0253

AC XY:

5190

AN XY:

205238

show subpopulations

African (AFR)

AF:

0.0743

AC:

871

AN:

11726

American (AMR)

AF:

0.0212

AC:

322

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.0586

AC:

709

AN:

12096

East Asian (EAS)

AF:

0.000145

AC:

AN:

27602

South Asian (SAS)

AF:

0.00923

AC:

303

AN:

32842

European-Finnish (FIN)

AF:

0.0153

AC:

362

AN:

23714

Middle Eastern (MID)

AF:

0.0355

AC:

AN:

1720

European-Non Finnish (NFE)

AF:

0.0284

AC:

6992

AN:

246542

Other (OTH)

AF:

0.0303

AC:

698

AN:

23046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

459

917

1376

1834

2293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0391

AC:

5952

AN:

152304

Hom.:

165

Cov.:

AF XY:

0.0376

AC XY:

2799

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0759

AC:

3155

AN:

41556

American (AMR)

AF:

0.0293

AC:

449

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0576

AC:

200

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.00849

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0136

AC:

144

AN:

10622

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0272

AC:

1852

AN:

68014

Other (OTH)

AF:

0.0435

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

289

578

868

1157

1446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0332

Hom.:

165

Bravo

AF:

0.0415

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.76

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over