dbSNP rs2302267: TLR7:c.-98-22T>G (chrX-12867459-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016562.4(TLR7):c.-98-22T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 604,443 control chromosomes in the GnomAD database, including 1,041 homozygotes. There are 13,252 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 0.054 ( 133 hom., 1895 hem., cov: 23)

Exomes 𝑓: 0.070 ( 908 hom. 11357 hem. )

Consequence

TLR7
NM_016562.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.941

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=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4 link	c.-98-22T>G		intron_variant	Intron 1 of 2	ENST00000380659.4	NP_057646.1	Q9NYK1B2R9N9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR7	ENST00000380659.4 link	c.-98-22T>G		intron_variant	Intron 1 of 2	1	NM_016562.4	ENSP00000370034.3		Q9NYK1
TLR7	ENST00000484204.1 link	n.-20T>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0540

AC:

6037

AN:

111874

Hom.:

133

Cov.:

AF XY:

0.0555

AC XY:

1888

AN XY:

34026

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.00146

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.0616

Gnomad EAS

AF:

0.0778

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0704

Gnomad MID

AF:

0.0502

Gnomad NFE

AF:

0.0630

Gnomad OTH

AF:

0.0418

GnomAD4 exome

AF:

0.0704

AC:

34675

AN:

492517

Hom.:

908

Cov.:

AF XY:

0.0763

AC XY:

11357

AN XY:

148921

show subpopulations

Gnomad4 AFR exome

AF:

0.0245

Gnomad4 AMR exome

AF:

0.0903

Gnomad4 ASJ exome

AF:

0.0708

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0740

Gnomad4 NFE exome

AF:

0.0638

Gnomad4 OTH exome

AF:

0.0641

GnomAD4 genome

AF:

0.0540

AC:

6043

AN:

111926

Hom.:

133

Cov.:

AF XY:

0.0556

AC XY:

1895

AN XY:

34090

show subpopulations

Gnomad4 AFR

AF:

0.0235

Gnomad4 AMR

AF:

0.0695

Gnomad4 ASJ

AF:

0.0616

Gnomad4 EAS

AF:

0.0778

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.0704

Gnomad4 NFE

AF:

0.0631

Gnomad4 OTH

AF:

0.0413

Alfa

AF:

0.0632

Hom.:

2255

Bravo

AF:

0.0531

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.2

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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