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GeneBe

rs864058

chrX-12887911-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_016562.4(TLR7):c.2403G>A(p.Thr801=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-12887911-G-A is Benign according to our data. Variant chrX-12887911-G-A is described in ClinVar as [Benign]. Clinvar id is 2127820.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-12887911-G-A is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.65 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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/exons MANE UniProt
TLR7NM_016562.4 linkuse as main transcriptc.2403G>A p.Thr801= synonymous_variant 3/3 ENST00000380659.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR7ENST00000380659.4 linkuse as main transcriptc.2403G>A p.Thr801= synonymous_variant 3/31 NM_016562.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.122
AC:
13528
AN:
111146
Hom.:
838
Cov.:
23
AF XY:
0.109
AC XY:
3623
AN XY:
33380
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
GnomAD3 exomes
AF:
0.0796
AC:
14579
AN:
183039
Hom.:
593
AF XY:
0.0773
AC XY:
5223
AN XY:
67581
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 SAS exome
AF:
0.0571
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.:
33
AF XY:
0.0815
AC XY:
29631
AN XY:
363539
show subpopulations
Gnomad4 AFR exome
AF:
0.245
Gnomad4 AMR exome
AF:
0.0541
Gnomad4 ASJ exome
AF:
0.0990
Gnomad4 EAS exome
AF:
0.0162
Gnomad4 SAS exome
AF:
0.0604
Gnomad4 FIN exome
AF:
0.0502
Gnomad4 NFE exome
AF:
0.0823
Gnomad4 OTH exome
AF:
0.0925
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.122
AC:
13533
AN:
111199
Hom.:
838
Cov.:
23
AF XY:
0.109
AC XY:
3631
AN XY:
33443
show subpopulations
Gnomad4 AFR
AF:
0.231
Gnomad4 AMR
AF:
0.0972
Gnomad4 ASJ
AF:
0.104
Gnomad4 EAS
AF:
0.00872
Gnomad4 SAS
AF:
0.0539
Gnomad4 FIN
AF:
0.0395
Gnomad4 NFE
AF:
0.0843
Gnomad4 OTH
AF:
0.122
Alfa
AF:
0.0905
Hom.:
4065
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
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
Cadd
Benign
0.073
Dann
Benign
0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs864058; hg19: chrX-12906030; COSMIC: COSV66125729; API