chr7-28955763-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014817.4(TRIL):​c.2284T>A​(p.Phe762Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000415 in 1,398,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

TRIL
NM_014817.4 missense

Scores

2
4
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1987328).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRILNM_014817.4 linkuse as main transcriptc.2284T>A p.Phe762Ile 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.2284T>A p.Phe762Ile missense_variant 1/1 NM_014817.4 ENSP00000479256 P1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000661
AC:
1
AN:
151230
Hom.:
0
AF XY:
0.0000124
AC XY:
1
AN XY:
80730
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000173
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000415
AC:
58
AN:
1398034
Hom.:
0
Cov.:
30
AF XY:
0.0000493
AC XY:
34
AN XY:
689556
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000519
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.00000378

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 GeneticsJul 09, 2021The c.2284T>A (p.F762I) alteration is located in exon 1 (coding exon 1) of the TRIL gene. This alteration results from a T to A substitution at nucleotide position 2284, causing the phenylalanine (F) at amino acid position 762 to be replaced by an isoleucine (I). 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
0.91
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
28
DANN
Benign
0.94
DEOGEN2
Benign
0.019
T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.73
T
MetaRNN
Benign
0.20
T
MutationAssessor
Benign
0.81
L
PrimateAI
Uncertain
0.78
T
Sift4G
Uncertain
0.011
D
Polyphen
0.96
P
Vest4
0.31
MVP
0.15
GERP RS
4.3
Varity_R
0.18
gMVP
0.56

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: rs1019972486; hg19: chr7-28995379; API