chr4-38801023-A-G

Variant names:

• chr4-38801023-A-G
• rs5743595
• NM_003263.4:c.-159-75T>C

Variant summary

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

The NM_003263.4(TLR1):​c.-159-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,644 control chromosomes in the GnomAD database, including 2,214 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 0.15 (2210 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4 hom.)
• Consequence: TLR1 NM_003263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 37 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]

ENSG00000306984 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 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.-159-75T>C		intron	N/A	NP_003254.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.-159-75T>C		intron	N/A	ENSP00000354932.2
	TLR1	ENST00000502213.7	TSL:1	c.-159-75T>C		intron	N/A	ENSP00000421259.1
	TLR1	ENST00000505940.1	TSL:3	c.-67-2125T>C		intron	N/A	ENSP00000421856.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22116 AN: 152084 Hom.: 2210 Cov.: 32

Gnomad AFR AF: 0.0343

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.100 AC: 44 AN: 440 Hom.: 4 AF XY: 0.124 AC XY: 33 AN XY: 266

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0981 AC: 42 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.145 AC: 22109 AN: 152204 Hom.: 2210 Cov.: 32 AF XY: 0.144 AC XY: 10713 AN XY: 74406

African (AFR) AF: 0.0342 AC: 1420 AN: 41540

American (AMR) AF: 0.173 AC: 2646 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1064 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2079 AN: 5168

South Asian (SAS) AF: 0.194 AC: 935 AN: 4826

European-Finnish (FIN) AF: 0.0823 AC: 873 AN: 10602

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12339 AN: 67994

Other (OTH) AF: 0.199 AC: 420 AN: 2108

Alfa AF: 0.153 Hom.: 355

Bravo AF: 0.151

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		0.26
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: rs5743595; hg19: chr4-38802644;