Variant chr6-41282728-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.46

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	UniProt
TREM1	NM_018643.5 linkuse as main transcript	c.73A>T	p.Thr25Ser	missense_variant	2/4	ENST00000244709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREM1	ENST00000244709.9 linkuse as main transcript	c.73A>T	p.Thr25Ser	missense_variant	2/4	1	NM_018643.5	P2	Q9NP99-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18108

AN:

152002

Hom.:

1221

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.106

AC XY:

77031

AN XY:

726812

show subpopulations

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.:

AF XY:

0.122

AC XY:

9046

AN XY:

74366

show subpopulations

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

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

LIST_S2

Benign

0.18

T;T;T;T

MetaRNN

Benign

0.0058

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;N;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.27

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over