4-38774682-T-C

Variant names:

• chr4-38774682-T-C
• rs11466652
• NM_030956.4:c.909A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_030956.4(TLR10):​c.909A>G​(p.Lys303Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,561,530 control chromosomes in the GnomAD database, including 17,830 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 0.18 (3057 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14773 hom.)
• Consequence: TLR10 NM_030956.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 23 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	NM_030956.4	MANE Select	c.909A>G	p.Lys303Lys	synonymous	Exon 4 of 4	NP_112218.2
	TLR10	NM_001017388.3		c.909A>G	p.Lys303Lys	synonymous	Exon 2 of 2	NP_001017388.1
	TLR10	NM_001195106.2		c.909A>G	p.Lys303Lys	synonymous	Exon 3 of 3	NP_001182035.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.909A>G	p.Lys303Lys	synonymous	Exon 4 of 4	ENSP00000308925.4
	TLR10	ENST00000361424.6	TSL:1	c.909A>G	p.Lys303Lys	synonymous	Exon 2 of 2	ENSP00000354459.2
	TLR10	ENST00000506111.1	TSL:1	c.909A>G	p.Lys303Lys	synonymous	Exon 2 of 2	ENSP00000421483.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28003 AN: 152034 Hom.: 3038 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.162 AC: 33316 AN: 205654 AF XY: 0.164

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.0755

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.106

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.137 AC: 193733 AN: 1409378 Hom.: 14773 Cov.: 35 AF XY: 0.140 AC XY: 97943 AN XY: 697354

African (AFR) AF: 0.294 AC: 9166 AN: 31128

American (AMR) AF: 0.0786 AC: 2604 AN: 33150

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 2709 AN: 22842

East Asian (EAS) AF: 0.0823 AC: 3235 AN: 39328

South Asian (SAS) AF: 0.208 AC: 15929 AN: 76706

European-Finnish (FIN) AF: 0.237 AC: 12231 AN: 51668

Middle Eastern (MID) AF: 0.224 AC: 1233 AN: 5498

European-Non Finnish (NFE) AF: 0.126 AC: 137906 AN: 1090918

Other (OTH) AF: 0.150 AC: 8720 AN: 58140

GnomAD4 genome AF: 0.184 AC: 28062 AN: 152152 Hom.: 3057 Cov.: 33 AF XY: 0.187 AC XY: 13914 AN XY: 74388

African (AFR) AF: 0.284 AC: 11791 AN: 41500

American (AMR) AF: 0.104 AC: 1595 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3472

East Asian (EAS) AF: 0.107 AC: 555 AN: 5188

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4828

European-Finnish (FIN) AF: 0.248 AC: 2620 AN: 10566

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9511 AN: 67988

Other (OTH) AF: 0.187 AC: 395 AN: 2114

Alfa AF: 0.151 Hom.: 3799

Bravo AF: 0.173

Asia WGS AF: 0.200 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.62
PhyloP100		-1.7
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: rs11466652; hg19: chr4-38776303; COSMIC: COSV58300525; COSMIC: COSV58300525;