4-38792853-T-TTATATATATATATATATATATATATATATATA

Position:

• chr4-38792853-T-TTATATATATATATATATATATATATATATATA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The XR_925163.3(TLR1):​n.4510_4511insTATATATATATATATATATATATATATATATA 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 0.00267 in 121,898 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.0027 (11 hom., cov: 24)
• Consequence: TLR1 XR_925163.3 non_coding_transcript_exon
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 326 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	XR_925163.3	n.4510_4511insTATATATATATATATATATATATATATATATA		non_coding_transcript_exon_variant	5/5
TLR1	XR_007057953.1	n.2659-1623_2659-1622insTATATATATATATATATATATATATATATATA		intron_variant, non_coding_transcript_variant
TLR1	XR_007057954.1	n.2567-1623_2567-1622insTATATATATATATATATATATATATATATATA		intron_variant, non_coding_transcript_variant
TLR1	XR_925165.3	n.2736-1623_2736-1622insTATATATATATATATATATATATATATATATA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLR1	ENST00000505744.5	n.236-1623_236-1622insTATATATATATATATATATATATATATATATA		intron_variant, non_coding_transcript_variant		3
TLR1	ENST00000510552.1	n.98-1623_98-1622insTATATATATATATATATATATATATATATATA		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 326 AN: 121862 Hom.: 11 Cov.: 24

Gnomad AFR AF: 0.00124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00278

Gnomad ASJ AF: 0.00573

Gnomad EAS AF: 0.00522

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.000500

Gnomad MID AF: 0.00442

Gnomad NFE AF: 0.00321

Gnomad OTH AF: 0.00697

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

GnomAD4 genome AF: 0.00267 AC: 326 AN: 121898 Hom.: 11 Cov.: 24 AF XY: 0.00266 AC XY: 157 AN XY: 59094

Gnomad4 AFR AF: 0.00124

Gnomad4 AMR AF: 0.00278

Gnomad4 ASJ AF: 0.00573

Gnomad4 EAS AF: 0.00524

Gnomad4 SAS AF: 0.00561

Gnomad4 FIN AF: 0.000500

Gnomad4 NFE AF: 0.00321

Gnomad4 OTH AF: 0.00694

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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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;