4-38777282-G-A

Variant names:

• chr4-38777282-G-A
• rs11466640
• NM_030956.4:c.-568-856C>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.-568-856C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,192 control chromosomes in the GnomAD database, including 1,958 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 0.14 (1958 hom., cov: 32)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 24 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	NM_030956.4	MANE Select	c.-568-856C>T		intron	N/A	NP_112218.2
	TLR10	NM_001017388.3		c.-62-1630C>T		intron	N/A	NP_001017388.1
	TLR10	NM_001195106.2		c.-379-856C>T		intron	N/A	NP_001182035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.-568-856C>T		intron	N/A	ENSP00000308925.4
	TLR10	ENST00000361424.6	TSL:1	c.-62-1630C>T		intron	N/A	ENSP00000354459.2
	TLR10	ENST00000613579.4	TSL:3	c.-379-856C>T		intron	N/A	ENSP00000478206.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20921 AN: 152074 Hom.: 1958 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.137 AC: 20913 AN: 152192 Hom.: 1958 Cov.: 32 AF XY: 0.135 AC XY: 10063 AN XY: 74400

African (AFR) AF: 0.0316 AC: 1314 AN: 41526

American (AMR) AF: 0.168 AC: 2563 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1723 AN: 5174

South Asian (SAS) AF: 0.182 AC: 876 AN: 4816

European-Finnish (FIN) AF: 0.0780 AC: 828 AN: 10612

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11933 AN: 68002

Other (OTH) AF: 0.187 AC: 395 AN: 2116

Alfa AF: 0.154 Hom.: 1181

Bravo AF: 0.143

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.48
PhyloP100		0.0090
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: rs11466640; hg19: chr4-38778903;