7-28955888-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014817.4(TRIL):ā€‹c.2159G>Cā€‹(p.Arg720Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,550,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 34)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

TRIL
NM_014817.4 missense

Scores

3
2
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.464
Variant links:
Genes affected
TRIL (HGNC:22200): (TLR4 interactor with leucine rich repeats) TRIL is a component of the TLR4 (MIM 603030) complex and is induced in a number of cell types by lipopolysaccharide (LPS) (Carpenter et al., 2009 [PubMed 19710467]).[supplied by OMIM, Apr 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRILNM_014817.4 linkuse as main transcriptc.2159G>C p.Arg720Pro missense_variant 1/1 ENST00000539664.3 NP_055632.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRILENST00000539664.3 linkuse as main transcriptc.2159G>C p.Arg720Pro missense_variant 1/1 NM_014817.4 ENSP00000479256 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152248
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000270
AC:
4
AN:
148408
Hom.:
0
AF XY:
0.0000500
AC XY:
4
AN XY:
80050
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000370
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000107
AC:
15
AN:
1398146
Hom.:
0
Cov.:
30
AF XY:
0.0000130
AC XY:
9
AN XY:
689866
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000363
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152366
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 15, 2023The c.2159G>C (p.R720P) alteration is located in exon 1 (coding exon 1) of the TRIL gene. This alteration results from a G to C substitution at nucleotide position 2159, causing the arginine (R) at amino acid position 720 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
27
DANN
Benign
0.90
DEOGEN2
Benign
0.036
T
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.77
T
MetaRNN
Uncertain
0.56
D
MutationAssessor
Benign
0.90
L
PrimateAI
Pathogenic
0.80
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.72
MVP
0.22
GERP RS
4.4
Varity_R
0.54
gMVP
0.87

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs898081664; hg19: chr7-28995504; API