Genetic Variant ENST00000505940.1:c.-129_-128insCT (chr4-38804814-A-AAG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000505940.1(TLR1):c.-129_-128insCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,236 control chromosomes in the GnomAD database, including 2,231 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2231 hom., cov: 30)

Failed GnomAD Quality Control

Consequence

TLR1
ENST00000505940.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.307

Publications

1 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000505940.1. 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.-298_-297insCT		upstream_gene	N/A	NP_003254.2

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
TLR1	ENST00000862584.1	c.-206_-205insCT	5_prime_UTR	Exon 2 of 4	ENSP00000532643.1
TLR1	ENST00000862585.1	c.-669_-668insCT	5_prime_UTR	Exon 1 of 3	ENSP00000532644.1
TLR1	ENST00000862586.1	c.-221_-220insCT	5_prime_UTR	Exon 1 of 3	ENSP00000532645.1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22230

AN:

152118

Hom.:

2231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0838

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.205

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.146

AC:

22223

AN:

152236

Hom.:

2231

Cov.:

AF XY:

0.145

AC XY:

10776

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0343

AC:

1426

AN:

41564

American (AMR)

AF:

0.174

AC:

2668

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1070

AN:

3470

East Asian (EAS)

AF:

0.402

AC:

2078

AN:

5168

South Asian (SAS)

AF:

0.196

AC:

945

AN:

4824

European-Finnish (FIN)

AF:

0.0838

AC:

889

AN:

10614

Middle Eastern (MID)

AF:

0.346

AC:

101

AN:

292

European-Non Finnish (NFE)

AF:

0.182

AC:

12376

AN:

67982

Other (OTH)

AF:

0.202

AC:

427

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

931

1861

2792

3722

4653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.148

Hom.:

230

Bravo

AF:

0.152

Asia WGS

AF:

0.235

AC:

816

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.31

BranchPoint Hunter

5.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over