rs11466640

chr4-38777282-G-Achr4-38777282-G-T

Variant summary

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

The NM_030956.4(TLR10):c.-568-856C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,192 control chromosomes in the GnomAD database, including 1,958 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 (1958 hom., cov: 32)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR10	NM_030956.4	c.-568-856C>T		intron_variant		ENST00000308973.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR10	ENST00000308973.9	c.-568-856C>T		intron_variant		5	NM_030956.4	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20921 AN: 152074 Hom.: 1958 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.137 AC: 20913 AN: 152192 Hom.: 1958 Cov.: 32 AF XY: 0.135 AC XY: 10063 AN XY: 74400

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.0780

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.187

Alfa AF: 0.153 Hom.: 1048

Bravo AF: 0.143

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.2
Dann	Benign	0.48

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: rs11466640; hg19: chr4-38778903;