4-38780799-G-A

Position:

• chr4-38780799-G-A

Variant summary

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

The NM_030956.4(TLR10):​c.-569+2122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,092 control chromosomes in the GnomAD database, including 9,905 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 0.33 (9905 hom., cov: 32)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR10	NM_030956.4	c.-569+2122C>T		intron_variant		ENST00000308973.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR10	ENST00000308973.9	c.-569+2122C>T		intron_variant		5	NM_030956.4	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50700 AN: 151972 Hom.: 9876 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.334 AC: 50785 AN: 152092 Hom.: 9905 Cov.: 32 AF XY: 0.332 AC XY: 24689 AN XY: 74362

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.387

Alfa AF: 0.292 Hom.: 2081

Bravo AF: 0.359

Asia WGS AF: 0.448 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.64

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: rs7658893; hg19: chr4-38782420;