4-38804391-A-G

Position:

• chr4-38804391-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003263.4(TLR1):​c.-236-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 152,278 control chromosomes in the GnomAD database, including 1,524 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 0.091 (1524 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLR1 NM_003263.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003311
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR1	NM_003263.4	c.-236-9T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000308979.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR1	ENST00000308979.7	c.-236-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003263.4	P1

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13761 AN: 152160 Hom.: 1519 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0802

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.0770

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.0905 AC: 13786 AN: 152278 Hom.: 1524 Cov.: 33 AF XY: 0.0945 AC XY: 7036 AN XY: 74462

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.00508

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0497 Hom.: 102

Bravo AF: 0.111

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00033
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.33		Position offset: -9

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743564; hg19: chr4-38806012;