chr4-38775552-A-T

Variant names:

• chr4-38775552-A-T
• rs10856838
• NM_030956.4:c.39T>A

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.39T>A​(p.Ile13Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,611,828 control chromosomes in the GnomAD database, including 35,810 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 0.27 (6921 hom., cov: 32)
  • Exomes 𝑓: 0.18 (28889 hom.)
• Consequence: TLR10 NM_030956.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 30 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=-0.86).
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 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.39T>A	p.Ile13Ile	synonymous	Exon 4 of 4	NP_112218.2
	TLR10	NM_001017388.3		c.39T>A	p.Ile13Ile	synonymous	Exon 2 of 2	NP_001017388.1
	TLR10	NM_001195106.2		c.39T>A	p.Ile13Ile	synonymous	Exon 3 of 3	NP_001182035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.39T>A	p.Ile13Ile	synonymous	Exon 4 of 4	ENSP00000308925.4
	TLR10	ENST00000361424.6	TSL:1	c.39T>A	p.Ile13Ile	synonymous	Exon 2 of 2	ENSP00000354459.2
	TLR10	ENST00000506111.1	TSL:1	c.39T>A	p.Ile13Ile	synonymous	Exon 2 of 2	ENSP00000421483.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41179 AN: 151938 Hom.: 6888 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.277

GnomAD2 exomes AF: 0.239 AC: 59402 AN: 248910 AF XY: 0.241

Gnomad AFR exome AF: 0.471

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.266

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.182 AC: 266028 AN: 1459772 Hom.: 28889 Cov.: 35 AF XY: 0.189 AC XY: 137035 AN XY: 726166

African (AFR) AF: 0.478 AC: 15964 AN: 33396

American (AMR) AF: 0.230 AC: 10178 AN: 44200

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5952 AN: 26026

East Asian (EAS) AF: 0.184 AC: 7290 AN: 39686

South Asian (SAS) AF: 0.367 AC: 31495 AN: 85884

European-Finnish (FIN) AF: 0.260 AC: 13865 AN: 53376

Middle Eastern (MID) AF: 0.345 AC: 1987 AN: 5758

European-Non Finnish (NFE) AF: 0.150 AC: 166292 AN: 1111118

Other (OTH) AF: 0.216 AC: 13005 AN: 60328

GnomAD4 genome AF: 0.271 AC: 41259 AN: 152056 Hom.: 6921 Cov.: 32 AF XY: 0.274 AC XY: 20403 AN XY: 74340

African (AFR) AF: 0.462 AC: 19119 AN: 41426

American (AMR) AF: 0.240 AC: 3672 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1044 AN: 5186

South Asian (SAS) AF: 0.363 AC: 1749 AN: 4820

European-Finnish (FIN) AF: 0.266 AC: 2813 AN: 10564

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11280 AN: 68006

Other (OTH) AF: 0.280 AC: 590 AN: 2108

Alfa AF: 0.202 Hom.: 1232

Bravo AF: 0.271

Asia WGS AF: 0.318 AC: 1109 AN: 3478

EpiCase AF: 0.168

EpiControl AF: 0.169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.2
DANN	Benign	0.69
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10856838; hg19: chr4-38777173; COSMIC: COSV58299181; COSMIC: COSV58299181;