X-12916993-G-T

Variant names:

• chrX-12916993-G-T
• rs5744069
• NM_138636.5:c.4-2051G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138636.5(TLR8):​c.4-2051G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 110,139 control chromosomes in the GnomAD database, including 9,546 homozygotes. There are 15,422 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 0.47 (9546 hom., 15422 hem., cov: 22)
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 6 publications found

Genes affected

TLR8 (HGNC:15632): (toll like receptor 8) 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. 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. The various TLRs exhibit different patterns of expression. This gene is predominantly expressed in lung and peripheral blood leukocytes, and lies in close proximity to another family member, TLR7, on chromosome X. [provided by RefSeq, Jul 2008]

TLR8-AS1 (HGNC:40720): (TLR8 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138636.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	NM_138636.5	MANE Select	c.4-2051G>T		intron	N/A	NP_619542.1
	TLR8	NM_016610.4		c.58-2051G>T		intron	N/A	NP_057694.2
	TLR8-AS1	NR_030727.1		n.241-8660C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	ENST00000218032.7	TSL:1 MANE Select	c.4-2051G>T		intron	N/A	ENSP00000218032.7
	TLR8	ENST00000311912.5	TSL:1	c.58-2051G>T		intron	N/A	ENSP00000312082.5

Frequencies

GnomAD3 genomes AF: 0.474 AC: 52231 AN: 110084 Hom.: 9544 Cov.: 22

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.428

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.475 AC: 52281 AN: 110139 Hom.: 9546 Cov.: 22 AF XY: 0.475 AC XY: 15422 AN XY: 32447

African (AFR) AF: 0.639 AC: 19254 AN: 30116

American (AMR) AF: 0.597 AC: 6184 AN: 10357

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 977 AN: 2631

East Asian (EAS) AF: 0.793 AC: 2770 AN: 3495

South Asian (SAS) AF: 0.618 AC: 1610 AN: 2606

European-Finnish (FIN) AF: 0.345 AC: 1995 AN: 5783

Middle Eastern (MID) AF: 0.437 AC: 94 AN: 215

European-Non Finnish (NFE) AF: 0.348 AC: 18379 AN: 52771

Other (OTH) AF: 0.489 AC: 734 AN: 1502

Alfa AF: 0.282 Hom.: 1544

Bravo AF: 0.505

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.41
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5744069; hg19: chrX-12935112;