NM_030956.4:c.-568-1047T>C

Variant names:

• chr4-38777473-A-G
• rs7694115
• NM_030956.4:c.-568-1047T>C

Variant summary

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

The NM_030956.4(TLR10):​c.-568-1047T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,890 control chromosomes in the GnomAD database, including 13,093 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 0.41 (13093 hom., cov: 31)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.-568-1047T>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.-568-1047T>C		intron_variant	Intron 1 of 3	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61603 AN: 151770 Hom.: 13058 Cov.: 31

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.406 AC: 61676 AN: 151890 Hom.: 13093 Cov.: 31 AF XY: 0.407 AC XY: 30198 AN XY: 74248

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.466

Alfa AF: 0.377 Hom.: 2338

Bravo AF: 0.411

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.35

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: rs7694115; hg19: chr4-38779094;