rs11466651

Variant names:

• chr4-38774699-C-T
• rs11466651
• NM_030956.4:c.892G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 28 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 (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 rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.892G>A	p.Val298Ile	missense_variant	Exon 4 of 4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.892G>A	p.Val298Ile	missense_variant	Exon 4 of 4	5	NM_030956.4	ENSP00000308925.4

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

GnomAD2 exomes AF: 0.0646 AC: 13774 AN: 213076 AF XY: 0.0663

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 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

African (AFR) AF: 0.0394 AC: 1237 AN: 31392

American (AMR) AF: 0.141 AC: 4846 AN: 34472

Ashkenazi Jewish (ASJ) AF: 0.0803 AC: 1879 AN: 23404

East Asian (EAS) AF: 0.101 AC: 3991 AN: 39416

South Asian (SAS) AF: 0.157 AC: 12239 AN: 78204

European-Finnish (FIN) AF: 0.0230 AC: 1199 AN: 52050

Middle Eastern (MID) AF: 0.113 AC: 627 AN: 5550

European-Non Finnish (NFE) AF: 0.0265 AC: 29103 AN: 1096288

Other (OTH) AF: 0.0544 AC: 3182 AN: 58516

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

African (AFR) AF: 0.0401 AC: 1666 AN: 41558

American (AMR) AF: 0.121 AC: 1844 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 291 AN: 3472

East Asian (EAS) AF: 0.0941 AC: 488 AN: 5184

South Asian (SAS) AF: 0.152 AC: 732 AN: 4822

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10608

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0293 AC: 1994 AN: 68026

Other (OTH) AF: 0.0686 AC: 145 AN: 2114

Alfa AF: 0.0404 Hom.: 582

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
LIST_S2	Benign	0.51	.;.;.;T;.;.
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
PhyloP100		-0.18
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
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: rs11466651; hg19: chr4-38776320; COSMIC: COSV58299173; COSMIC: COSV58299173;