chr4-38775615-T-G

Position:

• chr4-38775615-T-G

Variant summary

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

The NM_030956.4(TLR10):​c.-25A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,554,436 control chromosomes in the GnomAD database, including 33,644 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 0.27 (6920 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26724 hom.)
• Consequence: TLR10 NM_030956.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR10	NM_030956.4	c.-25A>C		5_prime_UTR_variant	4/4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.-25A>C		5_prime_UTR_variant	4/4	5	NM_030956.4	ENSP00000308925	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41166 AN: 151922 Hom.: 6887 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.278

GnomAD3 exomes AF: 0.238 AC: 49930 AN: 209778 Hom.: 6741 AF XY: 0.239 AC XY: 26928 AN XY: 112816

Gnomad AFR exome AF: 0.471

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.205

Gnomad SAS exome AF: 0.369

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.179 AC: 250431 AN: 1402394 Hom.: 26724 Cov.: 29 AF XY: 0.184 AC XY: 127845 AN XY: 692950

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.271 AC: 41246 AN: 152042 Hom.: 6920 Cov.: 32 AF XY: 0.274 AC XY: 20390 AN XY: 74320

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.281

Alfa AF: 0.196 Hom.: 4937

Bravo AF: 0.271

Asia WGS AF: 0.319 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.68

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: rs10856839; hg19: chr4-38777236; COSMIC: COSV58299188; COSMIC: COSV58299188;