Genetic Variant TLR9:p.Ala1031Ala (chr3-52221223-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_017442.4(TLR9):c.3093C>T(p.Ala1031Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,511,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

TLR9
NM_017442.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.73

Publications

2 publications found

Variant links:

Genes affected

TLR9 (HGNC:15633): (toll like receptor 9) 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. Studies in mice and human indicate that this receptor mediates cellular response to unmethylated CpG dinucleotides in bacterial DNA to mount an innate immune response. [provided by RefSeq, Aug 2017]

TLR9 links:

ENSG00000173366 (HGNC:):

ENSG00000173366 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-52221223-G-A is Benign according to our data. Variant chr3-52221223-G-A is described in ClinVar as Benign. ClinVar VariationId is 713902.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.72 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017442.4. 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
	TLR9	NM_017442.4	MANE Select	c.3093C>T	p.Ala1031Ala	synonymous	Exon 2 of 2	NP_059138.1	Q9NR96-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR9	ENST00000360658.3	TSL:1 MANE Select	c.3093C>T	p.Ala1031Ala	synonymous	Exon 2 of 2	ENSP00000353874.2	Q9NR96-1
	ENSG00000173366	ENST00000494383.1	TSL:2	c.3552C>T	p.Ala1184Ala	synonymous	Exon 5 of 5	ENSP00000417517.1	H0Y858

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000495

AC:

AN:

175818

AF XY:

0.000455

show subpopulations

Gnomad AFR exome

AF:

0.000457

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00440

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000697

Gnomad OTH exome

AF:

0.000753

GnomAD4 exome

AF:

0.000147

AC:

200

AN:

1358740

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

664252

show subpopulations

African (AFR)

AF:

0.000233

AC:

AN:

30038

American (AMR)

AF:

0.0000353

AC:

AN:

28302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19756

East Asian (EAS)

AF:

0.00219

AC:

AN:

38308

South Asian (SAS)

AF:

0.000186

AC:

AN:

69936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5280

European-Non Finnish (NFE)

AF:

0.0000744

AC:

AN:

1061534

Other (OTH)

AF:

0.000287

AC:

AN:

55832

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000348

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000529

AC:

AN:

41564

American (AMR)

AF:

0.0000654

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00444

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68028

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000185

Hom.:

Bravo

AF:

0.000400

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.12

(source)

DANN

Benign

0.48

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over