NM_014817.4:c.1925G>C

Variant names:

• chr7-28956122-C-G
• rs771705979
• NM_014817.4:c.1925G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014817.4(TRIL):​c.1925G>C​(p.Ser642Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,410,682 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: TRIL NM_014817.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.597
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043507546).

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.1925G>C	p.Ser642Thr	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.1925G>C	p.Ser642Thr	missense	Exon 1 of 1	ENSP00000479256.1	Q7L0X0
	CPVL-AS2	ENST00000749297.1		n.195+172C>G		intron	N/A
	CPVL-AS2	ENST00000749315.1		n.178+47C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000125 AC: 2 AN: 159728 AF XY: 0.0000115

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000315

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000135 AC: 19 AN: 1410682 Hom.: 0 Cov.: 30 AF XY: 0.0000129 AC XY: 9 AN XY: 697282

African (AFR) AF: 0.00 AC: 0 AN: 32296

American (AMR) AF: 0.00 AC: 0 AN: 37330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25372

East Asian (EAS) AF: 0.00 AC: 0 AN: 36794

South Asian (SAS) AF: 0.00 AC: 0 AN: 80236

European-Finnish (FIN) AF: 0.0000215 AC: 1 AN: 46560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.0000156 AC: 17 AN: 1087720

Other (OTH) AF: 0.0000170 AC: 1 AN: 58660

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000331 Hom.: 0

ExAC AF: 0.0000433 AC: 5

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	0.081
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	15
DANN	Benign	0.84
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.044	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.60
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.084
MVP		0.16
GERP RS		4.0
Varity_R		0.18
gMVP		0.27

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: rs771705979; hg19: chr7-28995738;