NM_138636.5:c.3+2931G>A

Variant names:

• chrX-12909640-G-A
• rs4830805
• NM_138636.5:c.3+2931G>A

Variant summary

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

The NM_138636.5(TLR8):​c.3+2931G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 110,800 control chromosomes in the GnomAD database, including 3,275 homozygotes. There are 8,910 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 0.27 (3275 hom., 8910 hem., cov: 23)
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	NM_138636.5	MANE Select	c.3+2931G>A		intron	N/A	NP_619542.1	Q9NR97-1
	TLR8	NM_016610.4		c.-80-666G>A		intron	N/A	NP_057694.2
	TLR8-AS1	NR_030727.1		n.241-1307C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	ENST00000218032.7	TSL:1 MANE Select	c.3+2931G>A		intron	N/A	ENSP00000218032.7	Q9NR97-1
	TLR8	ENST00000311912.5	TSL:1	c.-80-666G>A		intron	N/A	ENSP00000312082.5	Q9NR97-2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 29851 AN: 110744 Hom.: 3277 Cov.: 23

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.270 AC: 29870 AN: 110800 Hom.: 3275 Cov.: 23 AF XY: 0.269 AC XY: 8910 AN XY: 33062

African (AFR) AF: 0.231 AC: 7044 AN: 30441

American (AMR) AF: 0.365 AC: 3810 AN: 10446

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 877 AN: 2615

East Asian (EAS) AF: 0.784 AC: 2739 AN: 3492

South Asian (SAS) AF: 0.492 AC: 1277 AN: 2595

European-Finnish (FIN) AF: 0.182 AC: 1086 AN: 5959

Middle Eastern (MID) AF: 0.355 AC: 76 AN: 214

European-Non Finnish (NFE) AF: 0.232 AC: 12236 AN: 52853

Other (OTH) AF: 0.312 AC: 474 AN: 1517

Alfa AF: 0.244 Hom.: 2454

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.62
PhyloP100		0.063
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: rs4830805; hg19: chrX-12927759;