Genetic Variant NM_003263.4:c.-236-93A>G (chr4-38804475-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.-236-93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,246 control chromosomes in the GnomAD database, including 2,244 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 0.15 ( 2244 hom., cov: 33)

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: -0.164

Publications

15 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=-0.68).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	NM_003263.4 link	c.-236-93A>G		intron_variant	Intron 1 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.-236-93A>G		intron_variant	Intron 1 of 3	1	NM_003263.4	ENSP00000354932.2		Q15399

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22248

AN:

152128

Hom.:

2244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0840

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.204

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

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)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.146

AC:

22241

AN:

152246

Hom.:

2244

Cov.:

AF XY:

0.145

AC XY:

10792

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0343

AC:

1425

AN:

41544

American (AMR)

AF:

0.174

AC:

2666

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1064

AN:

3462

East Asian (EAS)

AF:

0.402

AC:

2082

AN:

5176

South Asian (SAS)

AF:

0.195

AC:

942

AN:

4820

European-Finnish (FIN)

AF:

0.0840

AC:

892

AN:

10616

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.182

AC:

12400

AN:

68022

Other (OTH)

AF:

0.201

AC:

425

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

915

1830

2745

3660

4575

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:

0.163

Hom.:

560

Bravo

AF:

0.152

Asia WGS

AF:

0.236

AC:

820

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.4

(source)

DANN

Benign

0.80

PhyloP100

-0.16

PromoterAI

0.031

Neutral

(source)

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