chr7-28955837-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014817.4(TRIL):ā€‹c.2210A>Gā€‹(p.His737Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,549,772 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00014 ( 0 hom., cov: 34)
Exomes š‘“: 0.00018 ( 2 hom. )

Consequence

TRIL
NM_014817.4 missense

Scores

2
3
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.037733972).
BS2
High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRILNM_014817.4 linkuse as main transcriptc.2210A>G p.His737Arg 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.2210A>G p.His737Arg missense_variant 1/1 NM_014817.4 ENSP00000479256 P1

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152176
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000315
AC:
47
AN:
149374
Hom.:
0
AF XY:
0.000450
AC XY:
36
AN XY:
79950
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000406
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00159
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000143
Gnomad OTH exome
AF:
0.000468
GnomAD4 exome
AF:
0.000180
AC:
252
AN:
1397478
Hom.:
2
Cov.:
30
AF XY:
0.000225
AC XY:
155
AN XY:
689256
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000841
Gnomad4 ASJ exome
AF:
0.0000398
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00144
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000100
Gnomad4 OTH exome
AF:
0.000328
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152294
Hom.:
0
Cov.:
34
AF XY:
0.000175
AC XY:
13
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000205
Hom.:
0
Bravo
AF:
0.0000982
ExAC
AF:
0.000183
AC:
13
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsSep 27, 2021The c.2210A>G (p.H737R) alteration is located in exon 1 (coding exon 1) of the TRIL gene. This alteration results from a A to G substitution at nucleotide position 2210, causing the histidine (H) at amino acid position 737 to be replaced by an arginine (R). 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
Uncertain
0.50
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Uncertain
-0.080
CADD
Pathogenic
26
DANN
Benign
0.88
DEOGEN2
Benign
0.026
T
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.74
T
MetaRNN
Benign
0.038
T
MutationAssessor
Benign
0.97
L
PrimateAI
Pathogenic
0.88
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.21
MVP
0.16
GERP RS
4.8
Varity_R
0.25
gMVP
0.78

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: rs552268645; hg19: chr7-28995453; API