Genetic Variant TLR1:c.-68+369G>A (chr4-38800488-C-T) – 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+369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 152,180 control chromosomes in the GnomAD database, including 33 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 0.010 ( 33 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: -0.265

Publications

0 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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new If you want to explore the variant's impact on the transcript NM_003263.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 (SAS) allele frequency at 95% confidence interval = 0.0737 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.-68+369G>A		intron	N/A	NP_003254.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLR1	ENST00000308979.7	TSL:1 MANE Select	c.-68+369G>A	intron	N/A	ENSP00000354932.2	Q15399
TLR1	ENST00000502213.7	TSL:1	c.-68+369G>A	intron	N/A	ENSP00000421259.1	Q15399
TLR1	ENST00000862584.1		c.-67-1590G>A	intron	N/A	ENSP00000532643.1

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1545

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.0683

Gnomad SAS

AF:

0.0796

Gnomad FIN

AF:

0.00434

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00666

Gnomad OTH

AF:

0.0182

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)

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)

AC:

AN:

GnomAD4 genome

AF:

0.0102

AC:

1548

AN:

152180

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

837

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

41526

American (AMR)

AF:

0.00706

AC:

108

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3466

East Asian (EAS)

AF:

0.0681

AC:

353

AN:

5182

South Asian (SAS)

AF:

0.0803

AC:

387

AN:

4820

European-Finnish (FIN)

AF:

0.00434

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00666

AC:

453

AN:

67994

Other (OTH)

AF:

0.0204

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

156

234

312

390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00858

Hom.:

Bravo

AF:

0.00887

Asia WGS

AF:

0.0850

AC:

300

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.78

(source)

DANN

Benign

0.56

PhyloP100

-0.27

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over