7-28955763-A-T

Variant names:

• chr7-28955763-A-T
• rs1019972486
• NM_014817.4:c.2284T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

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]

ACMG classification

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 rank	MANE	Protein	UniProt
TRIL	NM_014817.4	c.2284T>A	p.Phe762Ile	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.2284T>A	p.Phe762Ile	missense_variant	Exon 1 of 1	6	NM_014817.4	ENSP00000479256.1

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

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

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

Submissions by phenotype

not specified Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The 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

Other links and lift over

dbSNP: rs1019972486; hg19: chr7-28995379;