NM_003263.4:c.944C>T

Variant names:

• chr4-38797888-G-A
• rs5743613
• NM_003263.4:c.944C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003263.4(TLR1):​c.944C>T​(p.Pro315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000862 in 1,613,958 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0040 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: TLR1 NM_003263.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 22 publications found

Genes affected

TLR1 (HGNC:11847): (toll like receptor 1) 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 ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008791745).
• BS2: High AC in GnomAd4 at 606 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003263.4. 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
	TLR1	NM_003263.4	MANE Select	c.944C>T	p.Pro315Leu	missense	Exon 4 of 4	NP_003254.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.944C>T	p.Pro315Leu	missense	Exon 4 of 4	ENSP00000354932.2
	TLR1	ENST00000502213.7	TSL:1	c.944C>T	p.Pro315Leu	missense	Exon 4 of 4	ENSP00000421259.1
	TLR1	ENST00000505744.6	TSL:3	n.235+2969C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00399 AC: 607 AN: 152158 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00116 AC: 291 AN: 250610 AF XY: 0.000848

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000538 AC: 786 AN: 1461682 Hom.: 0 Cov.: 35 AF XY: 0.000479 AC XY: 348 AN XY: 727094

African (AFR) AF: 0.0123 AC: 411 AN: 33480

American (AMR) AF: 0.000850 AC: 38 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 60 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000176 AC: 196 AN: 1111842

Other (OTH) AF: 0.00114 AC: 69 AN: 60396

GnomAD4 genome AF: 0.00398 AC: 606 AN: 152276 Hom.: 2 Cov.: 33 AF XY: 0.00396 AC XY: 295 AN XY: 74452

African (AFR) AF: 0.0129 AC: 538 AN: 41556

American (AMR) AF: 0.00222 AC: 34 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68018

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00169 Hom.: 6

Bravo AF: 0.00448

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0118 AC: 52

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00135 AC: 164

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.69
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.23
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.062
Sift	Benign	0.065	T
Sift4G	Benign	0.12	T
Polyphen		0.028	B
Vest4		0.38
MVP		0.51
MPC		0.19
ClinPred		0.021	T
GERP RS		0.73
Varity_R		0.13
gMVP		0.41
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs5743613; hg19: chr4-38799509; COSMIC: COSV58304788; COSMIC: COSV58304788;