rs4321646

Variant names:

• chr4-38782343-G-A
• rs4321646
• NM_030956.4:c.-569+578C>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+578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,154 control chromosomes in the GnomAD database, including 2,849 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 0.15 (2849 hom., cov: 32)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.-569+578C>T		intron_variant	Intron 1 of 3	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.-569+578C>T		intron_variant	Intron 1 of 3	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22385 AN: 152036 Hom.: 2830 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0870

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.148 AC: 22446 AN: 152154 Hom.: 2849 Cov.: 32 AF XY: 0.146 AC XY: 10861 AN XY: 74394

African (AFR) AF: 0.347 AC: 14402 AN: 41454

American (AMR) AF: 0.103 AC: 1576 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3470

East Asian (EAS) AF: 0.0867 AC: 450 AN: 5192

South Asian (SAS) AF: 0.217 AC: 1048 AN: 4820

European-Finnish (FIN) AF: 0.0300 AC: 318 AN: 10606

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.0561 AC: 3814 AN: 68000

Other (OTH) AF: 0.174 AC: 368 AN: 2116

Alfa AF: 0.120 Hom.: 725

Bravo AF: 0.158

Asia WGS AF: 0.195 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.43
PhyloP100		0.023
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4321646; hg19: chr4-38783964;