rs11466619

Variant names:

• chr4-38778810-T-G
• rs11466619
• NM_030956.4:c.-568-2384A>C

Variant summary

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

The NM_030956.4(TLR10):​c.-568-2384A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 152,070 control chromosomes in the GnomAD database, including 1,190 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 0.095 (1190 hom., cov: 32)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 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.-568-2384A>C		intron	N/A	NP_112218.2
	TLR10	NM_001017388.3		c.-62-3158A>C		intron	N/A	NP_001017388.1
	TLR10	NM_001195106.2		c.-379-2384A>C		intron	N/A	NP_001182035.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.-568-2384A>C		intron	N/A	ENSP00000308925.4
	TLR10	ENST00000361424.6	TSL:1	c.-62-3158A>C		intron	N/A	ENSP00000354459.2
	TLR10	ENST00000613579.4	TSL:3	c.-379-2384A>C		intron	N/A	ENSP00000478206.1

Frequencies

GnomAD3 genomes AF: 0.0952 AC: 14460 AN: 151952 Hom.: 1186 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.0952 AC: 14484 AN: 152070 Hom.: 1190 Cov.: 32 AF XY: 0.0952 AC XY: 7076 AN XY: 74336

African (AFR) AF: 0.200 AC: 8287 AN: 41440

American (AMR) AF: 0.139 AC: 2119 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3472

East Asian (EAS) AF: 0.0946 AC: 490 AN: 5180

South Asian (SAS) AF: 0.153 AC: 738 AN: 4814

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: 0.0301 AC: 2046 AN: 67978

Other (OTH) AF: 0.0989 AC: 208 AN: 2104

Alfa AF: 0.0579 Hom.: 260

Bravo AF: 0.107

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.45
PhyloP100		-0.59
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: rs11466619; hg19: chr4-38780431;