dbSNP rs5743599: TLR1:c.-68+314C>T (chr4-38800543-G-A) – 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.-68+314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,010 control chromosomes in the GnomAD database, including 985 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 0.072 ( 985 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TLR1
NM_003263.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Publications

2 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:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4 link	c.-68+314C>T		intron_variant	Intron 3 of 3	ENST00000308979.7	NP_003254.2	Q15399

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000308979.7 link	c.-68+314C>T		intron_variant	Intron 3 of 3	1	NM_003263.4	ENSP00000354932.2		Q15399

Frequencies

GnomAD3 genomes

AF:

0.0716

AC:

10876

AN:

151888

Hom.:

981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0860

Gnomad FIN

AF:

0.00513

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00300

Gnomad OTH

AF:

0.0656

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

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:

0.0717

AC:

10899

AN:

152010

Hom.:

985

Cov.:

AF XY:

0.0764

AC XY:

5680

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.151

AC:

6253

AN:

41454

American (AMR)

AF:

0.203

AC:

3100

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3468

East Asian (EAS)

AF:

0.125

AC:

648

AN:

5178

South Asian (SAS)

AF:

0.0854

AC:

411

AN:

4814

European-Finnish (FIN)

AF:

0.00513

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00300

AC:

204

AN:

67970

Other (OTH)

AF:

0.0682

AC:

144

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

448

897

1345

1794

2242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0421

Hom.:

375

Bravo

AF:

0.0885

Asia WGS

AF:

0.124

AC:

431

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.52

(source)

DANN

Benign

0.77

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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