rs7658893

Variant names:

• chr4-38780799-G-A
• rs7658893
• NM_030956.4:c.-569+2122C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030956.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	NM_030956.4	MANE Select	c.-569+2122C>T		intron	N/A	NP_112218.2	Q9BXR5
	TLR10	NM_001017388.3		c.-63+2122C>T		intron	N/A	NP_001017388.1	Q9BXR5
	TLR10	NM_001195106.2		c.-380+2122C>T		intron	N/A	NP_001182035.1	Q9BXR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.-569+2122C>T		intron	N/A	ENSP00000308925.4	Q9BXR5
	TLR10	ENST00000361424.6	TSL:1	c.-63+2122C>T		intron	N/A	ENSP00000354459.2	Q9BXR5
	TLR10	ENST00000613579.4	TSL:3	c.-380+2122C>T		intron	N/A	ENSP00000478206.1	Q9BXR5

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

African (AFR) AF: 0.498 AC: 20666 AN: 41470

American (AMR) AF: 0.362 AC: 5525 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1475 AN: 3472

East Asian (EAS) AF: 0.504 AC: 2609 AN: 5178

South Asian (SAS) AF: 0.448 AC: 2160 AN: 4826

European-Finnish (FIN) AF: 0.114 AC: 1206 AN: 10598

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15954 AN: 67966

Other (OTH) AF: 0.387 AC: 817 AN: 2112

Alfa AF: 0.273 Hom.: 3092

Bravo AF: 0.359

Asia WGS AF: 0.448 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7658893; hg19: chr4-38782420;