chrX-12871908-T-A

Variant names:

• chrX-12871908-T-A
• rs1634322
• NM_016562.4:c.3+4327T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016562.4(TLR7):​c.3+4327T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 111,348 control chromosomes in the GnomAD database, including 2,055 homozygotes. There are 6,930 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 0.21 (2055 hom., 6930 hem., cov: 23)
• Consequence: TLR7 NM_016562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR7	NM_016562.4	c.3+4327T>A		intron_variant	Intron 2 of 2	ENST00000380659.4	NP_057646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR7	ENST00000380659.4	c.3+4327T>A		intron_variant	Intron 2 of 2	1	NM_016562.4	ENSP00000370034.3
TLR7	ENST00000484204.1	n.103+4327T>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 23922 AN: 111297 Hom.: 2058 Cov.: 23 AF XY: 0.207 AC XY: 6919 AN XY: 33501

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.215 AC: 23915 AN: 111348 Hom.: 2055 Cov.: 23 AF XY: 0.206 AC XY: 6930 AN XY: 33564

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.232

Alfa AF: 0.192 Hom.: 1149

Bravo AF: 0.222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.37

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: rs1634322; hg19: chrX-12890027;