rs2234237

Positions:

• chr6-41282728-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018643.5(TREM1):​c.73A>T​(p.Thr25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,174 control chromosomes in the GnomAD database, including 10,557 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.12 (1227 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9330 hom.)
• Consequence: TREM1 NM_018643.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.46

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]

TREM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005774379).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREM1	NM_018643.5	c.73A>T	p.Thr25Ser	missense_variant	2/4	ENST00000244709.9	NP_061113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREM1	ENST00000244709.9	c.73A>T	p.Thr25Ser	missense_variant	2/4	1	NM_018643.5	ENSP00000244709.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18108 AN: 152002 Hom.: 1221 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.130 AC: 32115 AN: 247794 Hom.: 2516 AF XY: 0.127 AC XY: 17098 AN XY: 134284

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.0931

Gnomad EAS exome AF: 0.303

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0961

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.106 AC: 154967 AN: 1461054 Hom.: 9330 Cov.: 32 AF XY: 0.106 AC XY: 77031 AN XY: 726812

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.0909

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.0943

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.119 AC: 18132 AN: 152120 Hom.: 1227 Cov.: 32 AF XY: 0.122 AC XY: 9046 AN XY: 74366

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0952

Gnomad4 OTH AF: 0.126

Alfa AF: 0.105 Hom.: 263

Bravo AF: 0.123

TwinsUK AF: 0.0914 AC: 339

ALSPAC AF: 0.0999 AC: 385

ESP6500AA AF: 0.125 AC: 549

ESP6500EA AF: 0.0941 AC: 809

ExAC AF: 0.128 AC: 15538

Asia WGS AF: 0.216 AC: 752 AN: 3478

EpiCase AF: 0.0962

EpiControl AF: 0.0965

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0010
DANN	Benign	0.068
DEOGEN2	Benign	0.063	.;T;.;.
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.7
FATHMM_MKL	Benign	0.00099	N
LIST_S2	Benign	0.18	T;T;T;T
MetaRNN	Benign	0.0058	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.13	.;N;N;.
REVEL	Benign	0.030
Sift	Benign	0.75	.;T;T;.
Sift4G	Benign	0.73	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.13
MutPred		0.14		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MPC		0.088
ClinPred		0.0019	T
GERP RS		-7.6
Varity_R		0.39
gMVP		0.098

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: rs2234237; hg19: chr6-41250466; COSMIC: COSV55148009; COSMIC: COSV55148009;