NM_030956.4:c.-569+2061G>C

Variant names:

• chr4-38780860-C-G
• rs7660429
• NM_030956.4:c.-569+2061G>C

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+2061G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,076 control chromosomes in the GnomAD database, including 2,181 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 (2181 hom., cov: 32)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 10 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.-569+2061G>C		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+2061G>C		intron_variant	Intron 1 of 3	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22868 AN: 151958 Hom.: 2168 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.00750

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.151 AC: 22921 AN: 152076 Hom.: 2181 Cov.: 32 AF XY: 0.152 AC XY: 11316 AN XY: 74336

African (AFR) AF: 0.232 AC: 9638 AN: 41482

American (AMR) AF: 0.0784 AC: 1199 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3468

East Asian (EAS) AF: 0.00732 AC: 38 AN: 5190

South Asian (SAS) AF: 0.0992 AC: 478 AN: 4820

European-Finnish (FIN) AF: 0.236 AC: 2484 AN: 10540

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8381 AN: 67972

Other (OTH) AF: 0.141 AC: 297 AN: 2108

Alfa AF: 0.157 Hom.: 299

Bravo AF: 0.140

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.13
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: rs7660429; hg19: chr4-38782481;