4-38792853-TTATATATATATA-TTATATATATATATATA

Variant names:

• chr4-38792853-T-TTATA
• rs72518392
• XR_925163.3:n.4507_4510dupTATA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The XR_925163.3(TLR1):​n.4507_4510dupTATA 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 0.0121 in 122,220 control chromosomes in the GnomAD database, including 90 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.012 (90 hom., cov: 24)
• Consequence: TLR1 XR_925163.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.891

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

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1474/122220) while in subpopulation AFR AF= 0.0352 (1164/33110). AF 95% confidence interval is 0.0335. There are 90 homozygotes in gnomad4. There are 718 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1474 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	XR_925163.3	n.4507_4510dupTATA		non_coding_transcript_exon_variant	Exon 5 of 5
TLR1	XR_007057953.1	n.2659-1626_2659-1623dupTATA		intron_variant	Intron 3 of 3
TLR1	XR_007057954.1	n.2567-1626_2567-1623dupTATA		intron_variant	Intron 2 of 2
TLR1	XR_925165.3	n.2736-1626_2736-1623dupTATA		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000505744.5	n.236-1623_236-1622insTATA		intron_variant	Intron 3 of 3	3
TLR1	ENST00000510552.1	n.98-1623_98-1622insTATA		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1475 AN: 122184 Hom.: 90 Cov.: 24

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00228

Gnomad EAS AF: 0.0155

Gnomad SAS AF: 0.0183

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00877

Gnomad NFE AF: 0.00158

Gnomad OTH AF: 0.0139

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0121 AC: 1474 AN: 122220 Hom.: 90 Cov.: 24 AF XY: 0.0121 AC XY: 718 AN XY: 59242

Gnomad4 AFR AF: 0.0352

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00228

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.0181

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00158

Gnomad4 OTH AF: 0.0138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72518392; hg19: chr4-38794474;