X-12916854-T-C

Variant names:

• chrX-12916854-T-C
• rs5744067
• NM_138636.5:c.4-2190T>C

Variant summary

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

The NM_138636.5(TLR8):​c.4-2190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 109,858 control chromosomes in the GnomAD database, including 2,084 homozygotes. There are 6,306 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 0.20 (2084 hom., 6306 hem., cov: 22)
• Consequence: TLR8 NM_138636.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 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.4-2190T>C		intron	N/A	NP_619542.1
	TLR8	NM_016610.4		c.58-2190T>C		intron	N/A	NP_057694.2
	TLR8-AS1	NR_030727.1		n.241-8521A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	ENST00000218032.7	TSL:1 MANE Select	c.4-2190T>C		intron	N/A	ENSP00000218032.7
	TLR8	ENST00000311912.5	TSL:1	c.58-2190T>C		intron	N/A	ENSP00000312082.5

Frequencies

GnomAD3 genomes AF: 0.196 AC: 21518 AN: 109802 Hom.: 2085 Cov.: 22

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.196 AC: 21524 AN: 109858 Hom.: 2084 Cov.: 22 AF XY: 0.196 AC XY: 6306 AN XY: 32142

African (AFR) AF: 0.106 AC: 3212 AN: 30252

American (AMR) AF: 0.306 AC: 3128 AN: 10226

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 526 AN: 2633

East Asian (EAS) AF: 0.747 AC: 2561 AN: 3429

South Asian (SAS) AF: 0.455 AC: 1170 AN: 2570

European-Finnish (FIN) AF: 0.128 AC: 736 AN: 5738

Middle Eastern (MID) AF: 0.229 AC: 48 AN: 210

European-Non Finnish (NFE) AF: 0.181 AC: 9554 AN: 52647

Other (OTH) AF: 0.227 AC: 337 AN: 1484

Alfa AF: 0.182 Hom.: 1728

Bravo AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.71
PhyloP100		0.020
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: rs5744067; hg19: chrX-12934973;