chr4-38778850-T-C

Position:

• chr4-38778850-T-C

Variant summary

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

The NM_030956.4(TLR10):​c.-568-2424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,244 control chromosomes in the GnomAD database, including 1,963 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 0.14 (1962 hom., cov: 32)
  • Exomes 𝑓: 0.18 (1 hom.)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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]

TLR10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR10	NM_030956.4	c.-568-2424A>G		intron_variant		ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.-568-2424A>G		intron_variant		5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20931 AN: 152104 Hom.: 1962 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.182 AC: 4 AN: 22 Hom.: 1 AF XY: 0.182 AC XY: 4 AN XY: 22

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.137 AC: 20923 AN: 152222 Hom.: 1962 Cov.: 32 AF XY: 0.135 AC XY: 10077 AN XY: 74426

Gnomad4 AFR AF: 0.0317

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.0780

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.186

Alfa AF: 0.131 Hom.: 254

Bravo AF: 0.143

Asia WGS AF: 0.193 AC: 670 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	7.4
DANN	Benign	0.69

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: rs11466617; hg19: chr4-38780471;