rs538009689

Variant names:

• chr7-28955858-C-G
• rs538009689
• NM_014817.4:c.2189G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-28955858-C-G
• chr7-28955858-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014817.4(TRIL):​c.2189G>C​(p.Arg730Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R730W) 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: 2.51
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33305168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIL	NM_014817.4	c.2189G>C	p.Arg730Pro	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.2189G>C	p.Arg730Pro	missense_variant	Exon 1 of 1	6	NM_014817.4	ENSP00000479256.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000675 AC: 1 AN: 148192 AF XY: 0.0000126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

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: 7.16e-7 AC: 1 AN: 1397510 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689316

African (AFR) AF: 0.00 AC: 0 AN: 31586

American (AMR) AF: 0.0000280 AC: 1 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25154

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078814

Other (OTH) AF: 0.00 AC: 0 AN: 57958

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Benign	0.92
DEOGEN2	Benign	0.040	T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.33	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.5
PrimateAI	Pathogenic	0.87	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.34
GERP RS		4.4
Varity_R		0.51
gMVP		0.81

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: rs538009689; hg19: chr7-28995474;