7-28956213-G-C

Variant names:

• chr7-28956213-G-C
• rs1009878108
• NM_014817.4:c.1834C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014817.4(TRIL):​c.1834C>G​(p.Pro612Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000769 in 1,560,540 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: TRIL NM_014817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09341326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIL	NM_014817.4	c.1834C>G	p.Pro612Ala	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.1834C>G	p.Pro612Ala	missense_variant	Exon 1 of 1	6	NM_014817.4	ENSP00000479256.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152260 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000648 AC: 1 AN: 154390 Hom.: 0 AF XY: 0.0000118 AC XY: 1 AN XY: 84810

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000639 AC: 9 AN: 1408162 Hom.: 0 Cov.: 32 AF XY: 0.0000115 AC XY: 8 AN XY: 695896

Gnomad4 AFR exome AF: 0.000279

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152378 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74514

Gnomad4 AFR AF: 0.0000721

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.023	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.093	T
MutationAssessor	Benign	0.97	L
PrimateAI	Pathogenic	0.83	D
Sift4G	Benign	0.33	T
Polyphen		0.24	B
Vest4		0.25
MVP		0.20
GERP RS		4.8
Varity_R		0.17
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs1009878108; hg19: chr7-28995829;