rs864058

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_016562.4(TLR7):c.2403G>A(p.Thr801Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 1,209,370 control chromosomes in the GnomAD database, including 3,807 homozygotes. There are 33,262 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 838 hom., 3631 hem., cov: 23)

Exomes 𝑓: 0.082 ( 2969 hom. 29631 hem. )

Consequence

TLR7
NM_016562.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65

Publications

32 publications found

Variant links:

Genes affected

TLR7 (HGNC:15631): (toll like receptor 7) 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. The human TLR family comprises 11 members. 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. For the recognition of structural components in foreign microorganisms, the various TLRs exhibit different patterns of expression as well; in this way for example, TLR-3, -7, and -8 are essential in the recognition of single-stranded RNA viruses. TLR7 senses single-stranded RNA oligonucleotides containing guanosine- and uridine-rich sequences from RNA viruses, a recognition occuring in the endosomes of plasmacytoid dendritic cells and B cells. This gene is predominantly expressed in lung, placenta, and spleen, and is phylogenetically related and lies in close proximity to another family member, TLR8, on chromosome X. [provided by RefSeq, Aug 2020]

TLR7 Gene-Disease associations (from GenCC):

systemic lupus erythematosus 17
Inheritance: XL Classification: MODERATE Submitted by: Baylor College of Medicine Research Center
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
immunodeficiency 74, COVID-19-related, X-linked
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TLR7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-12887911-G-A is Benign according to our data. Variant chrX-12887911-G-A is described in ClinVar as Benign. ClinVar VariationId is 2127820.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4 link	c.2403G>A	p.Thr801Thr	synonymous_variant	Exon 3 of 3	ENST00000380659.4	NP_057646.1	Q9NYK1B2R9N9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR7	ENST00000380659.4 link	c.2403G>A	p.Thr801Thr	synonymous_variant	Exon 3 of 3	1	NM_016562.4	ENSP00000370034.3		Q9NYK1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

13528

AN:

111146

Hom.:

838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.0975

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.00869

Gnomad SAS

AF:

0.0541

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0843

Gnomad OTH

AF:

0.123

GnomAD2 exomes

AF:

0.0796

AC:

14579

AN:

183039

AF XY:

0.0773

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.0484

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.00404

Gnomad FIN exome

AF:

0.0483

Gnomad NFE exome

AF:

0.0862

Gnomad OTH exome

AF:

0.0893

GnomAD4 exome

AF:

0.0821

AC:

90186

AN:

1098171

Hom.:

2969

Cov.:

AF XY:

0.0815

AC XY:

29631

AN XY:

363539

show subpopulations

African (AFR)

AF:

0.245

AC:

6459

AN:

26402

American (AMR)

AF:

0.0541

AC:

1904

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.0990

AC:

1919

AN:

19385

East Asian (EAS)

AF:

0.0162

AC:

488

AN:

30206

South Asian (SAS)

AF:

0.0604

AC:

3273

AN:

54145

European-Finnish (FIN)

AF:

0.0502

AC:

2035

AN:

40525

Middle Eastern (MID)

AF:

0.140

AC:

581

AN:

4137

European-Non Finnish (NFE)

AF:

0.0823

AC:

69265

AN:

842076

Other (OTH)

AF:

0.0925

AC:

4262

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

3522

7044

10567

14089

17611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2634

5268

7902

10536

13170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.122

AC:

13533

AN:

111199

Hom.:

838

Cov.:

AF XY:

0.109

AC XY:

3631

AN XY:

33443

show subpopulations

African (AFR)

AF:

0.231

AC:

7025

AN:

30462

American (AMR)

AF:

0.0972

AC:

1025

AN:

10541

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

275

AN:

2633

East Asian (EAS)

AF:

0.00872

AC:

AN:

3555

South Asian (SAS)

AF:

0.0539

AC:

142

AN:

2633

European-Finnish (FIN)

AF:

0.0395

AC:

236

AN:

5976

Middle Eastern (MID)

AF:

0.136

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.0843

AC:

4468

AN:

53006

Other (OTH)

AF:

0.122

AC:

183

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

422

843

1265

1686

2108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.105

Hom.:

7828

Bravo

AF:

0.133

EpiCase

AF:

0.0971

EpiControl

AF:

0.0990

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.073

(source)

DANN

Benign

0.58

PhyloP100

-1.7

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over