6-41282412-C-G

Variant names:

• chr6-41282412-C-G
• rs780834156
• NM_018643.5:c.389G>C

Variant summary

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

The NM_018643.5(TREM1):​c.389G>C​(p.Arg130Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,000 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. R130H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TREM1 NM_018643.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 2 publications found

Genes affected

TREM1 (HGNC:17760): (triggering receptor expressed on myeloid cells 1) This gene encodes a receptor belonging to the Ig superfamily that is expressed on myeloid cells. This protein amplifies neutrophil and monocyte-mediated inflammatory responses triggered by bacterial and fungal infections by stimulating release of pro-inflammatory chemokines and cytokines, as well as increased surface expression of cell activation markers. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jun 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018643.5. 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
	TREM1	NM_018643.5	MANE Select	c.389G>C	p.Arg130Pro	missense	Exon 2 of 4	NP_061113.1	Q38L15
	TREM1	NM_001242589.3		c.389G>C	p.Arg130Pro	missense	Exon 2 of 3	NP_001229518.1	Q9NP99-3
	TREM1	NM_001242590.3		c.389G>C	p.Arg130Pro	missense	Exon 2 of 3	NP_001229519.1	Q9NP99-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREM1	ENST00000244709.9	TSL:1 MANE Select	c.389G>C	p.Arg130Pro	missense	Exon 2 of 4	ENSP00000244709.3	Q9NP99-1
	TREM1	ENST00000591620.1	TSL:1	c.389G>C	p.Arg130Pro	missense	Exon 2 of 3	ENSP00000465345.1	Q9NP99-3
	TREM1	ENST00000334475.11	TSL:1	c.389G>C	p.Arg130Pro	missense	Exon 2 of 3	ENSP00000334284.5	Q9NP99-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249078 AF XY: 0.00

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: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459000 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725574

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25948

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5474

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110220

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000284 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0029	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.062
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.24
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.66		Loss of MoRF binding (P = 0.0627)
MVP		0.18
MPC		0.61
ClinPred		0.87	D
GERP RS		0.60
Varity_R		0.94
gMVP		0.87
Mutation Taster		=87/13	polymorphism

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: rs780834156; hg19: chr6-41250150;