rs11725309

Variant names:

• chr4-38782227-T-C
• rs11725309
• NM_030956.4:c.-569+694A>G

Variant summary

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

The NM_030956.4(TLR10):​c.-569+694A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,234 control chromosomes in the GnomAD database, including 2,154 homozygotes. 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 0.14 (2154 hom., cov: 32)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 18 publications found

Genes affected

TLR10 (HGNC:15634): (toll like receptor 10) 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 most highly expressed in lymphoid tissues such as spleen, lymph node, thymus, and tonsil. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030956.4. 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
	TLR10	NM_030956.4	MANE Select	c.-569+694A>G		intron	N/A	NP_112218.2	Q9BXR5
	TLR10	NM_001017388.3		c.-63+694A>G		intron	N/A	NP_001017388.1	Q9BXR5
	TLR10	NM_001195106.2		c.-380+694A>G		intron	N/A	NP_001182035.1	Q9BXR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.-569+694A>G		intron	N/A	ENSP00000308925.4	Q9BXR5
	TLR10	ENST00000361424.6	TSL:1	c.-63+694A>G		intron	N/A	ENSP00000354459.2	Q9BXR5
	TLR10	ENST00000613579.4	TSL:3	c.-380+694A>G		intron	N/A	ENSP00000478206.1	Q9BXR5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21904 AN: 152116 Hom.: 2154 Cov.: 32

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.0794

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.144 AC: 21896 AN: 152234 Hom.: 2154 Cov.: 32 AF XY: 0.142 AC XY: 10580 AN XY: 74444

African (AFR) AF: 0.0341 AC: 1418 AN: 41574

American (AMR) AF: 0.172 AC: 2633 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3468

East Asian (EAS) AF: 0.383 AC: 1988 AN: 5186

South Asian (SAS) AF: 0.191 AC: 918 AN: 4814

European-Finnish (FIN) AF: 0.0794 AC: 842 AN: 10600

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12298 AN: 67986

Other (OTH) AF: 0.198 AC: 419 AN: 2116

Alfa AF: 0.180 Hom.: 7747

Bravo AF: 0.150

Asia WGS AF: 0.230 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.66
PhyloP100		-0.089
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: rs11725309; hg19: chr4-38783848;