chr1-223110778-T-C

Variant names:

• chr1-223110778-T-C
• rs78098893
• NM_003268.6:c.2254A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003268.6(TLR5):​c.2254A>G​(p.Arg752Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000481 in 1,614,264 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: TLR5 NM_003268.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15
• Publications: 8 publications found

Genes affected

TLR5 (HGNC:11851): (toll like receptor 5) This gene encodes a member of the toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immune responses. These receptors recognize distinct pathogen-associated molecular patterns that are expressed on infectious agents. The protein encoded by this gene recognizes bacterial flagellin, the principal component of bacterial flagella and a virulence factor. The activation of this receptor mobilizes the nuclear factor NF-kappaB, which in turn activates a host of inflammatory-related target genes. Mutations in this gene have been associated with both resistance and susceptibility to systemic lupus erythematosus, and susceptibility to Legionnaire disease.[provided by RefSeq, Dec 2009]

ENSG00000299361 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0147899985).
• BP6: Variant 1-223110778-T-C is Benign according to our data. Variant chr1-223110778-T-C is described in ClinVar as [Benign]. Clinvar id is 791835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR5	NM_003268.6	c.2254A>G	p.Arg752Gly	missense_variant	Exon 6 of 6	ENST00000642603.2	NP_003259.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR5	ENST00000642603.2	c.2254A>G	p.Arg752Gly	missense_variant	Exon 6 of 6		NM_003268.6	ENSP00000496355.1

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 409 AN: 152262 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00931

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000712 AC: 179 AN: 251366 AF XY: 0.000537

Gnomad AFR exome AF: 0.00960

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000252 AC: 368 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.000198 AC XY: 144 AN XY: 727242

African (AFR) AF: 0.00854 AC: 286 AN: 33480

American (AMR) AF: 0.000559 AC: 25 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112004

Other (OTH) AF: 0.000695 AC: 42 AN: 60396

GnomAD4 genome AF: 0.00268 AC: 409 AN: 152380 Hom.: 3 Cov.: 32 AF XY: 0.00255 AC XY: 190 AN XY: 74520

African (AFR) AF: 0.00928 AC: 386 AN: 41586

American (AMR) AF: 0.00105 AC: 16 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000880 Hom.: 1

Bravo AF: 0.00295

ESP6500AA AF: 0.00885 AC: 39

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000964 AC: 117

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	20
DANN	Uncertain	1.0
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Pathogenic	0.98	D;.;.;D
MetaRNN	Benign	0.015	T;T;T;T
MetaSVM	Benign	-0.74	T
PhyloP100		1.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.1	D;.;D;.
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;.;D;.
Sift4G	Uncertain	0.0040	D;.;D;.
Vest4		0.76
MVP		0.59
MPC		0.39
ClinPred		0.081	T
GERP RS		2.1
gMVP		0.54
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs78098893; hg19: chr1-223284120;