chr6-41276147-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018643.5(TREM1):c.683C>T(p.Thr228Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
TREM1
NM_018643.5 missense
NM_018643.5 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 2.38
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREM1 | NM_018643.5 | c.683C>T | p.Thr228Met | missense_variant | 4/4 | ENST00000244709.9 | |
TREM1 | NM_001242590.3 | c.*37C>T | 3_prime_UTR_variant | 3/3 | |||
TREM1 | XM_011514696.3 | c.599+4814C>T | intron_variant | ||||
TREM1 | NR_136332.2 | n.710C>T | non_coding_transcript_exon_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREM1 | ENST00000244709.9 | c.683C>T | p.Thr228Met | missense_variant | 4/4 | 1 | NM_018643.5 | P2 | |
TREM1 | ENST00000334475.10 | c.*37C>T | 3_prime_UTR_variant | 3/3 | 1 | A2 | |||
TREM1 | ENST00000589614.5 | c.599+4814C>T | intron_variant | 2 | A2 | ||||
TREM1 | ENST00000589695.1 | n.358C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251410Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135878
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461826Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727224
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74440
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 21, 2021 | The c.683C>T (p.T228M) alteration is located in exon 4 (coding exon 4) of the TREM1 gene. This alteration results from a C to T substitution at nucleotide position 683, causing the threonine (T) at amino acid position 228 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of loop (P = 0.1242);
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at