rs4321646

chr4-38782343-G-A

Variant summary

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

The NM_030956.4(TLR10):c.-569+578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,154 control chromosomes in the GnomAD database, including 2,849 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 0.15 (2849 hom., cov: 32)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR10	NM_030956.4	c.-569+578C>T		intron_variant		ENST00000308973.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR10	ENST00000308973.9	c.-569+578C>T		intron_variant		5	NM_030956.4	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22385 AN: 152036 Hom.: 2830 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0870

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.148 AC: 22446 AN: 152154 Hom.: 2849 Cov.: 32 AF XY: 0.146 AC XY: 10861 AN XY: 74394

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0867

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0561

Gnomad4 OTH AF: 0.174

Alfa AF: 0.130 Hom.: 465

Bravo AF: 0.158

Asia WGS AF: 0.195 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.4
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4321646; hg19: chr4-38783964;