Genetic Variant TLR10:c.-138G>A (chr4-38775850-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030956.4(TLR10):c.-138G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 316,004 control chromosomes in the GnomAD database, including 5,639 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 ( 1957 hom., cov: 32)

Exomes 𝑓: 0.20 ( 3682 hom. )

Consequence

TLR10
NM_030956.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.113

Publications

31 publications found

Variant links:

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]

TLR10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4 link	c.-138G>A		5_prime_UTR_variant	Exon 3 of 4	ENST00000308973.9	NP_112218.2	Q9BXR5A0A024R9W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9 link	c.-138G>A		5_prime_UTR_variant	Exon 3 of 4	5	NM_030956.4	ENSP00000308925.4		Q9BXR5

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20908

AN:

151992

Hom.:

1957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.0785

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.195

AC:

31961

AN:

163894

Hom.:

3682

Cov.:

AF XY:

0.196

AC XY:

16678

AN XY:

85282

show subpopulations

African (AFR)

AF:

0.0393

AC:

188

AN:

4780

American (AMR)

AF:

0.154

AC:

1110

AN:

7224

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

1658

AN:

6042

East Asian (EAS)

AF:

0.433

AC:

5836

AN:

13486

South Asian (SAS)

AF:

0.184

AC:

1275

AN:

6934

European-Finnish (FIN)

AF:

0.0887

AC:

671

AN:

7566

Middle Eastern (MID)

AF:

0.270

AC:

215

AN:

796

European-Non Finnish (NFE)

AF:

0.179

AC:

19144

AN:

106688

Other (OTH)

AF:

0.180

AC:

1864

AN:

10378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1193

2387

3580

4774

5967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.137

AC:

20900

AN:

152110

Hom.:

1957

Cov.:

AF XY:

0.135

AC XY:

10061

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0315

AC:

1308

AN:

41498

American (AMR)

AF:

0.168

AC:

2569

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

956

AN:

3472

East Asian (EAS)

AF:

0.332

AC:

1717

AN:

5166

South Asian (SAS)

AF:

0.182

AC:

878

AN:

4816

European-Finnish (FIN)

AF:

0.0785

AC:

831

AN:

10582

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11924

AN:

67982

Other (OTH)

AF:

0.186

AC:

393

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

878

1756

2635

3513

4391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.181

Hom.:

3601

Bravo

AF:

0.143

Asia WGS

AF:

0.186

AC:

648

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.1

(source)

DANN

Benign

0.57

PhyloP100

0.11

PromoterAI

-0.038

Neutral

(source)

Mutation Taster

=297/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over