rs5743610

Variant names:

• chr4-38798718-G-A
• rs5743610
• NM_003263.4:c.114C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_003263.4(TLR1):​c.114C>T​(p.His38His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,613,594 control chromosomes in the GnomAD database, including 555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.018 (39 hom., cov: 32)
  • Exomes 𝑓: 0.024 (516 hom.)
• Consequence: TLR1 NM_003263.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.162
• Publications: 10 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=-0.89).
• BP6: Variant 4-38798718-G-A is Benign according to our data. Variant chr4-38798718-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056436.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.162 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0176 (2677/152280) while in subpopulation NFE AF = 0.0266 (1809/68012). AF 95% confidence interval is 0.0256. There are 39 homozygotes in GnomAd4. There are 1266 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2677 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	NM_003263.4	MANE Select	c.114C>T	p.His38His	synonymous	Exon 4 of 4	NP_003254.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.114C>T	p.His38His	synonymous	Exon 4 of 4	ENSP00000354932.2	Q15399
	TLR1	ENST00000502213.7	TSL:1	c.114C>T	p.His38His	synonymous	Exon 4 of 4	ENSP00000421259.1	Q15399
	TLR1	ENST00000862584.1		c.114C>T	p.His38His	synonymous	Exon 4 of 4	ENSP00000532643.1

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2676 AN: 152162 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.00456

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0273

GnomAD2 exomes AF: 0.0205 AC: 5139 AN: 250194 AF XY: 0.0211

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.0350

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.0310

Gnomad OTH exome AF: 0.0215

GnomAD4 exome AF: 0.0237 AC: 34701 AN: 1461314 Hom.: 516 Cov.: 33 AF XY: 0.0235 AC XY: 17098 AN XY: 726950

African (AFR) AF: 0.00415 AC: 139 AN: 33470

American (AMR) AF: 0.0139 AC: 622 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0330 AC: 861 AN: 26124

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39678

South Asian (SAS) AF: 0.00936 AC: 807 AN: 86190

European-Finnish (FIN) AF: 0.0151 AC: 804 AN: 53406

Middle Eastern (MID) AF: 0.0294 AC: 163 AN: 5548

European-Non Finnish (NFE) AF: 0.0270 AC: 30047 AN: 1111832

Other (OTH) AF: 0.0206 AC: 1242 AN: 60364

GnomAD4 genome AF: 0.0176 AC: 2677 AN: 152280 Hom.: 39 Cov.: 32 AF XY: 0.0170 AC XY: 1266 AN XY: 74470

African (AFR) AF: 0.00459 AC: 191 AN: 41572

American (AMR) AF: 0.0206 AC: 315 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.00766 AC: 37 AN: 4830

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10600

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0266 AC: 1809 AN: 68012

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0259 Hom.: 112

Bravo AF: 0.0172

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0264

EpiControl AF: 0.0279

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TLR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.38
PhyloP100		-0.16
Mutation Taster		=100/0	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: rs5743610; hg19: chr4-38800339;