4-38805707-A-G

Variant names:

• chr4-38805707-A-G
• rs45588337
• ENST00000822410.1:n.469A>G

Variant summary

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

The ENST00000822410.1(ENSG00000306984):​n.469A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,134 control chromosomes in the GnomAD database, including 2,254 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 (2252 hom., cov: 32)
  • Exomes 𝑓: 0.25 (2 hom.)
• Consequence: ENSG00000306984 ENST00000822410.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 13 publications found

Genes affected

ENSG00000306984 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000822410.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000306984	ENST00000822410.1		n.469A>G		non_coding_transcript_exon	Exon 2 of 2
	TLR1	ENST00000506146.5	TSL:4	c.-352-514T>C		intron	N/A	ENSP00000423725.1
	TLR1	ENST00000508364.1	TSL:4	c.-663T>C		upstream_gene	N/A	ENSP00000424894.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22265 AN: 151984 Hom.: 2252 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.250 AC: 8 AN: 32 Hom.: 2 AF XY: 0.333 AC XY: 8 AN XY: 24

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.227 AC: 5 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.146 AC: 22258 AN: 152102 Hom.: 2252 Cov.: 32 AF XY: 0.145 AC XY: 10796 AN XY: 74338

African (AFR) AF: 0.0344 AC: 1426 AN: 41504

American (AMR) AF: 0.174 AC: 2660 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3472

East Asian (EAS) AF: 0.403 AC: 2085 AN: 5172

South Asian (SAS) AF: 0.197 AC: 949 AN: 4824

European-Finnish (FIN) AF: 0.0839 AC: 887 AN: 10578

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12409 AN: 67964

Other (OTH) AF: 0.202 AC: 427 AN: 2110

Alfa AF: 0.152 Hom.: 288

Bravo AF: 0.152

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.51
DANN	Benign	0.58
PhyloP100		-0.99
PromoterAI		0.086	Neutral

Splicing

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

Other links and lift over

dbSNP: rs45588337; hg19: chr4-38807328;