4-38797314-C-T

Variant names:

• chr4-38797314-C-T
• rs5743614
• NM_003263.4:c.1518G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003263.4(TLR1):​c.1518G>A​(p.Ser506Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,613,154 control chromosomes in the GnomAD database, including 86,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.42 (17926 hom., cov: 31)
  • Exomes 𝑓: 0.27 (68101 hom.)
• Consequence: TLR1 NM_003263.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.13
• Publications: 23 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-38797314-C-T is Benign according to our data. Variant chr4-38797314-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059108.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

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.1518G>A	p.Ser506Ser	synonymous	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.1518G>A	p.Ser506Ser	synonymous	Exon 4 of 4	ENSP00000354932.2
	TLR1	ENST00000502213.7	TSL:1	c.1518G>A	p.Ser506Ser	synonymous	Exon 4 of 4	ENSP00000421259.1
	TLR1	ENST00000505744.6	TSL:3	n.235+3543G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64368 AN: 151766 Hom.: 17883 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.469

GnomAD2 exomes AF: 0.376 AC: 94350 AN: 250704 AF XY: 0.370

Gnomad AFR exome AF: 0.762

Gnomad AMR exome AF: 0.513

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.593

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.362

GnomAD4 exome AF: 0.270 AC: 394851 AN: 1461270 Hom.: 68101 Cov.: 37 AF XY: 0.276 AC XY: 200542 AN XY: 726948

African (AFR) AF: 0.756 AC: 24997 AN: 33066

American (AMR) AF: 0.508 AC: 22706 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 10571 AN: 26134

East Asian (EAS) AF: 0.632 AC: 25068 AN: 39684

South Asian (SAS) AF: 0.476 AC: 40983 AN: 86166

European-Finnish (FIN) AF: 0.124 AC: 6631 AN: 53418

Middle Eastern (MID) AF: 0.524 AC: 3021 AN: 5766

European-Non Finnish (NFE) AF: 0.217 AC: 241403 AN: 1111966

Other (OTH) AF: 0.323 AC: 19471 AN: 60352

GnomAD4 genome AF: 0.424 AC: 64466 AN: 151884 Hom.: 17926 Cov.: 31 AF XY: 0.424 AC XY: 31457 AN XY: 74258

African (AFR) AF: 0.756 AC: 31248 AN: 41346

American (AMR) AF: 0.498 AC: 7594 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3468

East Asian (EAS) AF: 0.595 AC: 3076 AN: 5166

South Asian (SAS) AF: 0.483 AC: 2318 AN: 4800

European-Finnish (FIN) AF: 0.114 AC: 1212 AN: 10590

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16147 AN: 67952

Other (OTH) AF: 0.472 AC: 993 AN: 2104

Alfa AF: 0.304 Hom.: 4615

Bravo AF: 0.467

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TLR1-related disorder Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.27
PhyloP100		-3.1
Mutation Taster		=96/4	polymorphism (auto)

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: rs5743614; hg19: chr4-38798935; COSMIC: COSV58303142; COSMIC: COSV58303142;