7-28956171-G-A

Variant summary

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

The NM_014817.4(TRIL):​c.1876C>T​(p.Arg626Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,574,908 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

TRIL
NM_014817.4 missense

Scores

5
3
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21
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 UniProt
TRILNM_014817.4 linkuse as main transcriptc.1876C>T p.Arg626Cys missense_variant 1/1 ENST00000539664.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRILENST00000539664.3 linkuse as main transcriptc.1876C>T p.Arg626Cys missense_variant 1/1 NM_014817.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000985
AC:
15
AN:
152232
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000626
AC:
11
AN:
175606
Hom.:
0
AF XY:
0.0000622
AC XY:
6
AN XY:
96502
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:
0.000152
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000160
AC:
228
AN:
1422676
Hom.:
0
Cov.:
30
AF XY:
0.000163
AC XY:
115
AN XY:
704118
show subpopulations
Gnomad4 AFR exome
AF:
0.0000306
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:
0.000197
Gnomad4 OTH exome
AF:
0.000186
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152232
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000177
Hom.:
0
Bravo
AF:
0.0000982
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000250
AC:
2
ExAC
AF:
0.0000775
AC:
9

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 GeneticsOct 25, 2022The c.1876C>T (p.R626C) alteration is located in exon 1 (coding exon 1) of the TRIL gene. This alteration results from a C to T substitution at nucleotide position 1876, causing the arginine (R) at amino acid position 626 to be replaced by a cysteine (C). 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
0.90
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
32
DANN
Benign
0.97
DEOGEN2
Benign
0.030
T
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.90
D
MetaRNN
Uncertain
0.47
T
MutationAssessor
Benign
0.97
L
PrimateAI
Pathogenic
0.90
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.53
MVP
0.49
GERP RS
4.9
Varity_R
0.28
gMVP
0.66

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: rs368229653; hg19: chr7-28995787; API