4-38774682-T-C

Position:

• chr4-38774682-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_030956.4(TLR10):​c.909A>G​(p.Lys303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,561,530 control chromosomes in the GnomAD database, including 17,830 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 0.18 (3057 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14773 hom.)
• Consequence: TLR10 NM_030956.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR10	NM_030956.4	c.909A>G	p.Lys303=	synonymous_variant	4/4	ENST00000308973.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR10	ENST00000308973.9	c.909A>G	p.Lys303=	synonymous_variant	4/4	5	NM_030956.4	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28003 AN: 152034 Hom.: 3038 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.162 AC: 33316 AN: 205654 Hom.: 3110 AF XY: 0.164 AC XY: 18120 AN XY: 110398

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.0755

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.216

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.137 AC: 193733 AN: 1409378 Hom.: 14773 Cov.: 35 AF XY: 0.140 AC XY: 97943 AN XY: 697354

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.0786

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0823

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.184 AC: 28062 AN: 152152 Hom.: 3057 Cov.: 33 AF XY: 0.187 AC XY: 13914 AN XY: 74388

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.187

Alfa AF: 0.148 Hom.: 2992

Bravo AF: 0.173

Asia WGS AF: 0.200 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.62

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: rs11466652; hg19: chr4-38776303; COSMIC: COSV58300525; COSMIC: COSV58300525;