dbSNP rs5743553: TLR1:c.-524T>A (chr4-38805568-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000508364.1(TLR1):c.-524T>A 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 0.0521 in 152,212 control chromosomes in the GnomAD database, including 484 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 0.052 ( 484 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TLR1
ENST00000508364.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.288

Publications

3 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:

ENSG00000306984 (HGNC:):

ENSG00000306984 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
TLR1	XM_005262662.6 link	c.-727T>A	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	XP_005262719.1	Q15399
TLR1	XM_011513742.4 link	c.-650T>A	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	XP_011512044.1	Q15399
TLR1	XM_011513745.4 link	c.-558T>A	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	XP_011512047.1	Q15399

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TLR1	ENST00000508364.1 link	c.-524T>A	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	4	ENSP00000424894.1	D6RF68
ENSG00000306984	ENST00000822410.1 link	n.330A>T	non_coding_transcript_exon_variant	Exon 2 of 2
TLR1	ENST00000508364.1 link	c.-524T>A	5_prime_UTR_variant	Exon 1 of 2	4	ENSP00000424894.1	D6RF68

Frequencies

GnomAD3 genomes

AF:

0.0520

AC:

7903

AN:

152094

Hom.:

478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0265

Gnomad ASJ

AF:

0.0283

Gnomad EAS

AF:

0.0720

Gnomad SAS

AF:

0.0904

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00880

Gnomad OTH

AF:

0.0541

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0521

AC:

7936

AN:

152212

Hom.:

484

Cov.:

AF XY:

0.0522

AC XY:

3884

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.140

AC:

5797

AN:

41472

American (AMR)

AF:

0.0264

AC:

404

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

AN:

3468

East Asian (EAS)

AF:

0.0715

AC:

371

AN:

5186

South Asian (SAS)

AF:

0.0901

AC:

434

AN:

4818

European-Finnish (FIN)

AF:

0.00885

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00880

AC:

599

AN:

68030

Other (OTH)

AF:

0.0606

AC:

128

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

344

688

1031

1375

1719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0330

Hom.:

Bravo

AF:

0.0564

Asia WGS

AF:

0.116

AC:

404

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.7

(source)

DANN

Benign

0.66

PhyloP100

0.29

PromoterAI

-0.039

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over