7-28955993-G-A

Variant names:

• chr7-28955993-G-A
• NM_014817.4:c.2054C>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.2054C>T​(p.Pro685Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,888 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: 0.0000029 (0 hom.)
• Consequence: TRIL NM_014817.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18
• 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=0.23895591).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014817.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIL	NM_014817.4	MANE Select	c.2054C>T	p.Pro685Leu	missense	Exon 1 of 1	NP_055632.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIL	ENST00000539664.3	TSL:6 MANE Select	c.2054C>T	p.Pro685Leu	missense	Exon 1 of 1	ENSP00000479256.1	Q7L0X0
	CPVL-AS2	ENST00000749315.1		n.96G>A		non_coding_transcript_exon	Exon 1 of 4
	CPVL-AS2	ENST00000749329.1		n.100G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1399888 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 691886

African (AFR) AF: 0.00 AC: 0 AN: 32044

American (AMR) AF: 0.00 AC: 0 AN: 37314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25222

East Asian (EAS) AF: 0.00 AC: 0 AN: 36456

South Asian (SAS) AF: 0.00 AC: 0 AN: 79812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1085880

Other (OTH) AF: 0.00 AC: 0 AN: 58406

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	29
DANN	Benign	0.97
DEOGEN2	Benign	0.068	T
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.24	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.2
PrimateAI	Uncertain	0.74	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.33
MVP		0.27
GERP RS		5.0
Varity_R		0.25
gMVP		0.39

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

hg19: chr7-28995609;