NM_001318789.2:c.-162-601A>G

Variant names:

• chr4-153687301-A-G
• rs1898830
• NM_001318789.2:c.-162-601A>G

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_001318789.2(TLR2):c.-162-601A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.308 (AC=46,871) in the gnomAD database across 152,062 control chromosomes, including 8,193 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.522. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8193 hom., cov: 32)
• Consequence: TLR2 NM_001318789.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 4 publications found

Genes affected

TLR2 (HGNC:11848): (toll like receptor 2) 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. This protein is a cell-surface protein that can form heterodimers with other TLR family members to recognize conserved molecules derived from microorganisms known as pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to an up-regulation of signaling pathways to modulate the host's inflammatory response. This gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene has been implicated in the pathogenesis of several autoimmune diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5217 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001318789.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TLR2 NM_001318789.2	MANE Select	c.-162-601A>G	intron	Intron 1 of 2	Prot: NP_001305718.1 UniProt:
	TLR2 NM_001318787.2		c.-372-616A>G	intron	Intron 1 of 3	Prot: NP_001305716.1 UniProt:
	TLR2 NM_001318790.2		c.-162-601A>G	intron	Intron 1 of 2	Prot: NP_001305719.1 UniProt:

TLR2 NM_001318789.2

MANE Select

HGVSc / HGVSpc.-162-601A>G

Exon rankIntron 1 of 2

intron

Prot: NP_001305718.1UniProt: O60603A0A0S2Z4S4

TLR2 NM_001318787.2

HGVSc / HGVSpc.-372-616A>G

Exon rankIntron 1 of 3

intron

Prot: NP_001305716.1UniProt: A0A0S2Z4S4O60603

TLR2 NM_001318790.2

HGVSc / HGVSpc.-162-601A>G

Exon rankIntron 1 of 2

intron

Prot: NP_001305719.1UniProt: O60603A0A0S2Z4S4

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TLR2 ENST00000642700.2	MANE Select	c.-162-601A>G	intron	Intron 1 of 2	Prot: ENSP00000494425.1 UniProt:
	TLR2 ENST00000260010.7	TSL:6	c.-1554-601A>G	intron	Intron 1 of 2	Prot: ENSP00000260010.6 UniProt:
	TLR2 ENST00000642580.1		c.-88-616A>G	intron	Intron 1 of 2	Prot: ENSP00000495339.1 UniProt:

TLR2 ENST00000642700.2

MANE Select

HGVSc / HGVSpc.-162-601A>G

Exon rankIntron 1 of 2

intron

Prot: ENSP00000494425.1UniProt: O60603

TLR2 ENST00000260010.7

TSL:6

HGVSc / HGVSpc.-1554-601A>G

Exon rankIntron 1 of 2

intron

Prot: ENSP00000260010.6UniProt: O60603

TLR2 ENST00000642580.1

HGVSc / HGVSpc.-88-616A>G

Exon rankIntron 1 of 2

intron

Prot: ENSP00000495339.1UniProt: O60603

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.308	AC:46841	Hom:8176	AN:151942	Cov:32
GnomAD4 genome	AF: 0.308	AC:46871	Hom:8193	AN:152062	Cov:32
TOPMed (Bravo)	AF: 0.307	AC:81240	Hom:14593	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.325	AC:28081	Hom:4993	AN:86508	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.322	AC:755	Hom:114	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.425	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.377	AC:113	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.477	AC:1650	Hom:	AN:3460	Cov:
Korea4K (4,157 Koreans)	AF: 0.447	AC:3225	Hom:	AN:7218	Cov:
Qatari Genome	AF: 0.239	AC:42	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.455	AC:55730	Hom:12739	AN:122508	Cov:
Turkish Variome	AF: 0.422	AC:652	Hom:136	AN:1546	Cov:
UK10K	AF: 0.345	AC:2612	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.427	AC:3824	Hom:816	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	4.9
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.5
DANN	Benign	0.89
GPN-Star LLR	N/A	-0.55
GPN-Star score	N/A	0.55
PhyloP100	Benign	-0.32

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs1898830;

hg19: chr4-154608453;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar