chr7-28955645-C-G

Variant names:

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

Variant summary

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

The NM_014817.4(TRIL):​c.2402G>C​(p.Arg801Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,393,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000043 (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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIL	NM_014817.4	c.2402G>C	p.Arg801Pro	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>C	p.Arg801Pro	missense_variant	Exon 1 of 1	6	NM_014817.4	ENSP00000479256.1
CPVL-AS2	ENST00000749297.1	n.-111C>G		upstream_gene_variant
CPVL-AS2	ENST00000749329.1	n.-249C>G		upstream_gene_variant
CPVL-AS2	ENST00000749333.1	n.-233C>G		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000431 AC: 6 AN: 1393572 Hom.: 0 Cov.: 30 AF XY: 0.00000291 AC XY: 2 AN XY: 687362

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

American (AMR) AF: 0.00 AC: 0 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: 0.0000126 AC: 1 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: 0.00000464 AC: 5 AN: 1078256

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

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.68	T
MetaRNN	Uncertain	0.45	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.6
PrimateAI	Uncertain	0.64	T
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.56
MVP		0.24
GERP RS		4.8
Varity_R		0.37
gMVP		0.67

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;