chr4-38796255-T-C

Variant names:

• chr4-38796255-T-C
• rs4624663
• NM_003263.4:c.*216A>G

Variant summary

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

The NM_003263.4(TLR1):​c.*216A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 546,750 control chromosomes in the GnomAD database, including 368 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 0.039 (165 hom., cov: 32)
  • Exomes 𝑓: 0.026 (203 hom.)
• Consequence: TLR1 NM_003263.4 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003263.4. 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
	TLR1	NM_003263.4	MANE Select	c.*216A>G		splice_region	Exon 4 of 4	NP_003254.2
	TLR1	NM_003263.4	MANE Select	c.*216A>G		3_prime_UTR	Exon 4 of 4	NP_003254.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.*216A>G		splice_region	Exon 4 of 4	ENSP00000354932.2
	TLR1	ENST00000308979.7	TSL:1 MANE Select	c.*216A>G		3_prime_UTR	Exon 4 of 4	ENSP00000354932.2
	TLR1	ENST00000502213.7	TSL:1	c.*216A>G		3_prime_UTR	Exon 4 of 4	ENSP00000421259.1

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5942 AN: 152186 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0294

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0439

GnomAD4 exome AF: 0.0262 AC: 10322 AN: 394446 Hom.: 203 Cov.: 5 AF XY: 0.0253 AC XY: 5190 AN XY: 205238

African (AFR) AF: 0.0743 AC: 871 AN: 11726

American (AMR) AF: 0.0212 AC: 322 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.0586 AC: 709 AN: 12096

East Asian (EAS) AF: 0.000145 AC: 4 AN: 27602

South Asian (SAS) AF: 0.00923 AC: 303 AN: 32842

European-Finnish (FIN) AF: 0.0153 AC: 362 AN: 23714

Middle Eastern (MID) AF: 0.0355 AC: 61 AN: 1720

European-Non Finnish (NFE) AF: 0.0284 AC: 6992 AN: 246542

Other (OTH) AF: 0.0303 AC: 698 AN: 23046

GnomAD4 genome AF: 0.0391 AC: 5952 AN: 152304 Hom.: 165 Cov.: 32 AF XY: 0.0376 AC XY: 2799 AN XY: 74480

African (AFR) AF: 0.0759 AC: 3155 AN: 41556

American (AMR) AF: 0.0293 AC: 449 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4828

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0272 AC: 1852 AN: 68014

Other (OTH) AF: 0.0435 AC: 92 AN: 2116

Alfa AF: 0.0332 Hom.: 165

Bravo AF: 0.0415

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.76
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4624663; hg19: chr4-38797876;