dbSNP rs45588337: ENSG00000306984:n.469A>G (chr4-38805707-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000822410.1(ENSG00000306984):n.469A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,134 control chromosomes in the GnomAD database, including 2,254 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 ( 2252 hom., cov: 32)

Exomes 𝑓: 0.25 ( 2 hom. )

Consequence

ENSG00000306984
ENST00000822410.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.989

Publications

13 publications found

Variant links:

Genes affected

ENSG00000306984 (HGNC:):

ENSG00000306984 links:

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=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
TLR1	XM_005262662.6 link	c.-866T>C	upstream_gene_variant	XP_005262719.1
TLR1	XM_011513742.4 link	c.-789T>C	upstream_gene_variant	XP_011512044.1
TLR1	XM_011513745.4 link	c.-697T>C	upstream_gene_variant	XP_011512047.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
ENSG00000306984	ENST00000822410.1 link	n.469A>G	non_coding_transcript_exon_variant	Exon 2 of 2
TLR1	ENST00000506146.5 link	c.-352-514T>C	intron_variant	Intron 1 of 5	4	ENSP00000423725.1
TLR1	ENST00000508364.1 link	c.-663T>C	upstream_gene_variant		4	ENSP00000424894.1
TLR1	ENST00000508535.1 link	n.-174T>C	upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22265

AN:

151984

Hom.:

2252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.0839

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.205

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.227

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.663

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.146

AC:

22258

AN:

152102

Hom.:

2252

Cov.:

AF XY:

0.145

AC XY:

10796

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0344

AC:

1426

AN:

41504

American (AMR)

AF:

0.174

AC:

2660

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1072

AN:

3472

East Asian (EAS)

AF:

0.403

AC:

2085

AN:

5172

South Asian (SAS)

AF:

0.197

AC:

949

AN:

4824

European-Finnish (FIN)

AF:

0.0839

AC:

887

AN:

10578

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12409

AN:

67964

Other (OTH)

AF:

0.202

AC:

427

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

932

1865

2797

3730

4662

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:

0.152

Hom.:

288

Bravo

AF:

0.152

Asia WGS

AF:

0.235

AC:

816

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.51

(source)

DANN

Benign

0.58

PhyloP100

-0.99

PromoterAI

0.086

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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