rs11466651

chr4-38774699-C-T

Variant summary

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

The NM_030956.4(TLR10):c.892G>A(p.Val298Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,571,560 control chromosomes in the GnomAD database, including 2,753 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.048 (327 hom., cov: 33)
  • Exomes 𝑓: 0.041 (2426 hom.)
• Consequence: TLR10 NM_030956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012404621).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR10	NM_030956.4	c.892G>A	p.Val298Ile	missense_variant	4/4	ENST00000308973.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR10	ENST00000308973.9	c.892G>A	p.Val298Ile	missense_variant	4/4	5	NM_030956.4	P1

Frequencies

GnomAD3 genomes AF: 0.0483 AC: 7355 AN: 152150 Hom.: 320 Cov.: 33

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.0937

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0693

GnomAD3 exomes AF: 0.0646 AC: 13774 AN: 213076 Hom.: 734 AF XY: 0.0663 AC XY: 7596 AN XY: 114636

Gnomad AFR exome AF: 0.0388

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.0749

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.151

Gnomad FIN exome AF: 0.0207

Gnomad NFE exome AF: 0.0325

Gnomad OTH exome AF: 0.0672

GnomAD4 exome AF: 0.0411 AC: 58303 AN: 1419292 Hom.: 2426 Cov.: 36 AF XY: 0.0444 AC XY: 31278 AN XY: 703670

Gnomad4 AFR exome AF: 0.0394

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.0803

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.0230

Gnomad4 NFE exome AF: 0.0265

Gnomad4 OTH exome AF: 0.0544

GnomAD4 genome AF: 0.0484 AC: 7368 AN: 152268 Hom.: 327 Cov.: 33 AF XY: 0.0510 AC XY: 3798 AN XY: 74456

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.0941

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0686

Alfa AF: 0.0403 Hom.: 251

Bravo AF: 0.0531

TwinsUK AF: 0.0240 AC: 89

ALSPAC AF: 0.0291 AC: 112

ESP6500AA AF: 0.0395 AC: 174

ESP6500EA AF: 0.0277 AC: 238

ExAC AF: 0.0672 AC: 8158

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	6.5
Dann	Uncertain	0.99
DEOGEN2	Benign	0.017	T;T;T;T;T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.13	N
MetaRNN	Benign	0.0012	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M;M;M;M;M;M
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.33	N;.;N;.;N;N
REVEL	Benign	0.18
Sift	Benign	0.17	T;.;T;.;T;T
Sift4G	Benign	0.26	T;T;T;T;T;T
Polyphen		0.14	B;B;B;B;B;B
Vest4		0.092
MPC		0.061
ClinPred		0.0058	T
GERP RS		3.2
Varity_R		0.060
gMVP		0.092

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: rs11466651; hg19: chr4-38776320; COSMIC: COSV58299173; COSMIC: COSV58299173;