rs10004195

Variant names:

• chr4-38783103-T-A
• rs10004195
• NM_030956.4:c.-751A>T

Variant summary

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

The NM_030956.4(TLR10):​c.-751A>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,100 control chromosomes in the GnomAD database, including 7,208 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 0.29 (7208 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TLR10 NM_030956.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.-751A>T		upstream_gene_variant		ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.-751A>T		upstream_gene_variant		5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44609 AN: 151982 Hom.: 7188 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.294 AC: 44666 AN: 152100 Hom.: 7208 Cov.: 32 AF XY: 0.291 AC XY: 21622 AN XY: 74372

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.372

Alfa AF: 0.259 Hom.: 752

Bravo AF: 0.309

Asia WGS AF: 0.426 AC: 1483 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.68
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10004195; hg19: chr4-38784724;