Variant rs3853839 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016562.4(TLR7):c.*881C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 112,689 control chromosomes in the GnomAD database, including 2,614 homozygotes. There are 8,314 hemizygotes in GnomAD. 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 0.23 ( 2585 hom., 8253 hem., cov: 24)

Exomes 𝑓: 0.25 ( 29 hom. 61 hem. )

Consequence

TLR7
NM_016562.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR7	NM_016562.4 link	c.*881C>G		3_prime_UTR_variant	3/3	ENST00000380659.4	NP_057646.1	Q9NYK1B2R9N9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR7	ENST00000380659.4 link	c.*881C>G		3_prime_UTR_variant	3/3	1	NM_016562.4	ENSP00000370034.3		Q9NYK1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

25661

AN:

111721

Hom.:

2586

Cov.:

AF XY:

0.243

AC XY:

8239

AN XY:

33939

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.779

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.246

AC:

227

AN:

922

Hom.:

Cov.:

AF XY:

0.270

AC XY:

AN XY:

226

show subpopulations

Gnomad4 AFR exome

AF:

0.348

Gnomad4 AMR exome

AF:

0.563

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.650

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.230

AC:

25676

AN:

111767

Hom.:

2585

Cov.:

AF XY:

0.243

AC XY:

8253

AN XY:

33995

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.398

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.778

Gnomad4 SAS

AF:

0.525

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.184

Hom.:

1083

Bravo

AF:

0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.27

DANN

Benign

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over