NM_030956.4:c.-569+2321C>G

Variant names:

• chr4-38780600-G-C
• rs7653908
• NM_030956.4:c.-569+2321C>G

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+2321C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,052 control chromosomes in the GnomAD database, including 3,931 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 0.22 (3931 hom., cov: 32)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 14 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.-569+2321C>G		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+2321C>G		intron_variant	Intron 1 of 3	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33128 AN: 151934 Hom.: 3921 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.218 AC: 33165 AN: 152052 Hom.: 3931 Cov.: 32 AF XY: 0.214 AC XY: 15938 AN XY: 74328

African (AFR) AF: 0.248 AC: 10260 AN: 41434

American (AMR) AF: 0.212 AC: 3234 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1802 AN: 5168

South Asian (SAS) AF: 0.230 AC: 1106 AN: 4816

European-Finnish (FIN) AF: 0.0922 AC: 976 AN: 10590

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13813 AN: 67976

Other (OTH) AF: 0.267 AC: 562 AN: 2106

Alfa AF: 0.201 Hom.: 421

Bravo AF: 0.231

Asia WGS AF: 0.253 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.59
PhyloP100		-0.68
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: rs7653908; hg19: chr4-38782221;