NM_014817.4:c.2402G>T

Variant names:

• chr7-28955645-C-A
• rs928892673
• NM_014817.4:c.2402G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014817.4(TRIL):​c.2402G>T​(p.Arg801Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R801Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TRIL NM_014817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 0 publications found

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]

CPVL-AS2 (HGNC:56138): (CPVL antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14362222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIL	NM_014817.4	c.2402G>T	p.Arg801Leu	missense_variant	Exon 1 of 1	ENST00000539664.3	NP_055632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIL	ENST00000539664.3	c.2402G>T	p.Arg801Leu	missense_variant	Exon 1 of 1	6	NM_014817.4	ENSP00000479256.1
CPVL-AS2	ENST00000749297.1	n.-111C>A		upstream_gene_variant
CPVL-AS2	ENST00000749329.1	n.-249C>A		upstream_gene_variant
CPVL-AS2	ENST00000749333.1	n.-233C>A		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000681 AC: 1 AN: 146942 AF XY: 0.0000127

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000408

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 7.18e-7 AC: 1 AN: 1393572 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 687362

African (AFR) AF: 0.00 AC: 0 AN: 31578

American (AMR) AF: 0.0000281 AC: 1 AN: 35620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 35702

South Asian (SAS) AF: 0.00 AC: 0 AN: 79078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078256

Other (OTH) AF: 0.00 AC: 0 AN: 57904

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.0089	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.14	T
MutationAssessor	Benign	0.46	N
PhyloP100		1.6
PrimateAI	Uncertain	0.64	T
Sift4G	Benign	0.15	T
Polyphen		0.034	B
Vest4		0.47
MVP		0.24
GERP RS		4.8
Varity_R		0.17
gMVP		0.60

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

Other links and lift over

dbSNP: rs928892673; hg19: chr7-28995261;