7-28956431-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014817.4(TRIL):​c.1616C>A​(p.Ala539Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,540,590 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

TRIL
NM_014817.4 missense

Scores

2
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.575
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.012168497).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRILNM_014817.4 linkuse as main transcriptc.1616C>A p.Ala539Glu 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.1616C>A p.Ala539Glu missense_variant 1/1 NM_014817.4 ENSP00000479256 P1

Frequencies

GnomAD3 genomes
AF:
0.000217
AC:
33
AN:
152232
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000426
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000176
AC:
24
AN:
136708
Hom.:
0
AF XY:
0.000173
AC XY:
13
AN XY:
75254
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000797
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:
0.000412
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000218
AC:
303
AN:
1388358
Hom.:
1
Cov.:
32
AF XY:
0.000226
AC XY:
155
AN XY:
685844
show subpopulations
Gnomad4 AFR exome
AF:
0.0000635
Gnomad4 AMR exome
AF:
0.000110
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:
0.000256
Gnomad4 OTH exome
AF:
0.000241
GnomAD4 genome
AF:
0.000217
AC:
33
AN:
152232
Hom.:
0
Cov.:
34
AF XY:
0.000202
AC XY:
15
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000426
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000431
Hom.:
0
Bravo
AF:
0.000166
ESP6500AA
AF:
0.000368
AC:
1
ESP6500EA
AF:
0.000649
AC:
4
ExAC
AF:
0.0000749
AC:
8

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 GeneticsMar 21, 2023The c.1616C>A (p.A539E) alteration is located in exon 1 (coding exon 1) of the TRIL gene. This alteration results from a C to A substitution at nucleotide position 1616, causing the alanine (A) at amino acid position 539 to be replaced by a glutamic acid (E). 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
Benign
0.086
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
0.54
DANN
Benign
0.53
DEOGEN2
Benign
0.0051
T
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.43
T
MetaRNN
Benign
0.012
T
MutationAssessor
Benign
0.55
N
PrimateAI
Uncertain
0.68
T
Sift4G
Benign
0.72
T
Polyphen
0.047
B
Vest4
0.079
MVP
0.12
GERP RS
-0.29
Varity_R
0.060
gMVP
0.19

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: rs375849614; hg19: chr7-28996047; API