chr4-153691494-T-C

Variant names:

• chr4-153691494-T-C
• rs4585282
• NM_001318789.2:c.-17+3447T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318789.2(TLR2):​c.-17+3447T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,304 control chromosomes in the GnomAD database, including 70,953 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 0.96 (70953 hom., cov: 32)
• Consequence: TLR2 NM_001318789.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR2	NM_001318789.2	c.-17+3447T>C		intron_variant	Intron 2 of 2	ENST00000642700.2	NP_001305718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR2	ENST00000642700.2	c.-17+3447T>C		intron_variant	Intron 2 of 2		NM_001318789.2	ENSP00000494425.1

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146703 AN: 152186 Hom.: 70896 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.995

Gnomad OTH AF: 0.969

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.964 AC: 146818 AN: 152304 Hom.: 70953 Cov.: 32 AF XY: 0.965 AC XY: 71897 AN XY: 74482

African (AFR) AF: 0.887 AC: 36813 AN: 41526

American (AMR) AF: 0.983 AC: 15040 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3457 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5181 AN: 5182

South Asian (SAS) AF: 0.996 AC: 4813 AN: 4834

European-Finnish (FIN) AF: 0.998 AC: 10598 AN: 10622

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.995 AC: 67679 AN: 68040

Other (OTH) AF: 0.970 AC: 2052 AN: 2116

Alfa AF: 0.973 Hom.: 9326

Bravo AF: 0.959

Asia WGS AF: 0.984 AC: 3422 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs4585282; hg19: chr4-154612646;