4-38792853-TTATATATATATA-TTATATATATATATATATATATATATATATATATATATA

Variant names:

• chr4-38792853-T-TTATATATATATATATATATATATATA
• rs72518392
• XR_925163.3:n.4510_4511insTATATATATATATATATATATATATA

Variant summary

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

The XR_925163.3(TLR1):​n.4510_4511insTATATATATATATATATATATATATA 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 0.0279 in 120,514 control chromosomes in the GnomAD database, including 155 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.028 (155 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 nfe. gnomad4 allele frequency = 0.0279 (3362/120514) while in subpopulation NFE AF= 0.0389 (2169/55828). AF 95% confidence interval is 0.0375. There are 155 homozygotes in gnomad4. There are 1489 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3362 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR1	XR_925163.3	n.4510_4511insTATATATATATATATATATATATATA		non_coding_transcript_exon_variant	Exon 5 of 5
TLR1	XR_007057953.1	n.2659-1623_2659-1622insTATATATATATATATATATATATATA		intron_variant	Intron 3 of 3
TLR1	XR_007057954.1	n.2567-1623_2567-1622insTATATATATATATATATATATATATA		intron_variant	Intron 2 of 2
TLR1	XR_925165.3	n.2736-1623_2736-1622insTATATATATATATATATATATATATA		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_236-1622insTATATATATATATATATATATATATA		intron_variant	Intron 3 of 3	3
TLR1	ENST00000510552.1	n.98-1623_98-1622insTATATATATATATATATATATATATA		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 3365 AN: 120478 Hom.: 155 Cov.: 24

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.0575

Gnomad EAS AF: 0.0203

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.00619

Gnomad MID AF: 0.0472

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0334

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

GnomAD4 genome AF: 0.0279 AC: 3362 AN: 120514 Hom.: 155 Cov.: 24 AF XY: 0.0255 AC XY: 1489 AN XY: 58420

Gnomad4 AFR AF: 0.0169

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.0575

Gnomad4 EAS AF: 0.0203

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.00619

Gnomad4 NFE AF: 0.0389

Gnomad4 OTH AF: 0.0326

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;