7-28956201-C-T

Variant names:

• chr7-28956201-C-T
• rs778837240
• NM_014817.4:c.1846G>A

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.1846G>A​(p.Gly616Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,413,330 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. G616R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TRIL NM_014817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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=0.21083888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIL	NM_014817.4	c.1846G>A	p.Gly616Ser	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.1846G>A	p.Gly616Ser	missense_variant	Exon 1 of 1	6	NM_014817.4	ENSP00000479256.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1413330 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 698800

African (AFR) AF: 0.00 AC: 0 AN: 32332

American (AMR) AF: 0.00 AC: 0 AN: 38142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25018

East Asian (EAS) AF: 0.00 AC: 0 AN: 37462

South Asian (SAS) AF: 0.00 AC: 0 AN: 80440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089458

Other (OTH) AF: 0.00 AC: 0 AN: 58636

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.21	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.82	D
Sift4G	Benign	0.085	T
Polyphen		0.99	D
Vest4		0.24
MVP		0.17
GERP RS		4.8
Varity_R		0.26
gMVP		0.33

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

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Other links and lift over

dbSNP: rs778837240; hg19: chr7-28995817;