chrX-12885540-A-T

Position:

chrX-12885540-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016562.4(TLR7):c.32A>T(p.Gln11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,202,693 control chromosomes in the GnomAD database, including 17,131 homozygotes. There are 75,300 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.18 ( 1401 hom., 5934 hem., cov: 23)

Exomes 𝑓: 0.20 ( 15730 hom. 69366 hem. )

Consequence

TLR7
NM_016562.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.150

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031428337).

BP6

Variant X-12885540-A-T is Benign according to our data. Variant chrX-12885540-A-T is described in ClinVar as [Benign]. Clinvar id is 2015182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR7	NM_016562.4 linkuse as main transcript	c.32A>T	p.Gln11Leu	missense_variant	3/3	ENST00000380659.4	NP_057646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR7	ENST00000380659.4 linkuse as main transcript	c.32A>T	p.Gln11Leu	missense_variant	3/3	1	NM_016562.4	ENSP00000370034	P1

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

20199

AN:

111447

Hom.:

1402

Cov.:

AF XY:

0.176

AC XY:

5933

AN XY:

33639

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.0674

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.178

AC:

31777

AN:

178823

Hom.:

2171

AF XY:

0.176

AC XY:

11187

AN XY:

63623

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.000145

Gnomad SAS exome

AF:

0.0765

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.198

AC:

216392

AN:

1091191

Hom.:

15730

Cov.:

AF XY:

0.194

AC XY:

69366

AN XY:

357607

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.192

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.000332

Gnomad4 SAS exome

AF:

0.0783

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.181

AC:

20191

AN:

111502

Hom.:

1401

Cov.:

AF XY:

0.176

AC XY:

5934

AN XY:

33704

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.000279

Gnomad4 SAS

AF:

0.0665

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.200

Hom.:

5320

Bravo

AF:

0.177

TwinsUK

AF:

0.217

AC:

806

ALSPAC

AF:

0.207

AC:

598

ESP6500AA

AF:

0.136

AC:

521

ESP6500EA

AF:

0.212

AC:

1429

ExAC

AF:

0.174

AC:

21109

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.89

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.79

DANN

Benign

0.94

DEOGEN2

Benign

0.082

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.67

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.54

REVEL

Benign

0.036

Sift

Benign

0.094

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.029

MPC

0.68

ClinPred

0.012

GERP RS

-5.4

Varity_R

0.072

gMVP

0.50

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over