rs5741881

Positions:

• chrX-12888595-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_016562.4(TLR7):​c.3087A>G​(p.Leu1029=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,209,543 control chromosomes in the GnomAD database, including 968 homozygotes. There are 3,635 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.059 (461 hom., 1735 hem., cov: 23)
  • Exomes 𝑓: 0.0066 (507 hom. 1900 hem.)
• Consequence: TLR7 NM_016562.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-12888595-A-G is Benign according to our data. Variant chrX-12888595-A-G is described in ClinVar as [Benign]. Clinvar id is 2039041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR7	NM_016562.4	c.3087A>G	p.Leu1029=	synonymous_variant	3/3	ENST00000380659.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR7	ENST00000380659.4	c.3087A>G	p.Leu1029=	synonymous_variant	3/3	1	NM_016562.4	P1

Frequencies

GnomAD3 genomes AF: 0.0590 AC: 6581 AN: 111530 Hom.: 461 Cov.: 23 AF XY: 0.0509 AC XY: 1718 AN XY: 33734

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000749

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00844

Gnomad NFE AF: 0.000659

Gnomad OTH AF: 0.0463

GnomAD3 exomes AF: 0.0173 AC: 3166 AN: 183196 Hom.: 212 AF XY: 0.0118 AC XY: 799 AN XY: 67646

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.00979

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000421

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.00841

GnomAD4 exome AF: 0.00656 AC: 7198 AN: 1097959 Hom.: 507 Cov.: 32 AF XY: 0.00523 AC XY: 1900 AN XY: 363319

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.0119

Gnomad4 ASJ exome AF: 0.0000516

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000499

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000295

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.0591 AC: 6600 AN: 111584 Hom.: 461 Cov.: 23 AF XY: 0.0513 AC XY: 1735 AN XY: 33798

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.0209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000751

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000659

Gnomad4 OTH AF: 0.0457

Alfa AF: 0.0374 Hom.: 285

Bravo AF: 0.0693

EpiCase AF: 0.000436

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.3
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs5741881; hg19: chrX-12906714;