Variant 6-41282397-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018643.5(TREM1):c.404A>C(p.Lys135Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,605,342 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0064 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 13 hom. )

Consequence

TREM1
NM_018643.5 missense, splice_region

Scores

Splicing: ADA: 0.00004585

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.822

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058051646).

BP6

Variant 6-41282397-T-G is Benign according to our data. Variant chr6-41282397-T-G is described in ClinVar as [Benign]. Clinvar id is 723369.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00644 (980/152214) while in subpopulation AFR AF= 0.0223 (928/41574). AF 95% confidence interval is 0.0211. There are 7 homozygotes in gnomad4. There are 472 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREM1	NM_018643.5 linkuse as main transcript	c.404A>C	p.Lys135Thr	missense_variant, splice_region_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.404A>C	p.Lys135Thr	missense_variant, splice_region_variant	2/4	1	NM_018643.5	P2	Q9NP99-1

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

973

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00175

AC:

432

AN:

246894

Hom.:

AF XY:

0.00128

AC XY:

170

AN XY:

133272

show subpopulations

Gnomad AFR exome

AF:

0.0243

Gnomad AMR exome

AF:

0.00102

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:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000630

AC:

916

AN:

1453128

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

386

AN XY:

721796

show subpopulations

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.00108

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000584

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.0000136

Gnomad4 OTH exome

AF:

0.00127

GnomAD4 genome

AF:

0.00644

AC:

980

AN:

152214

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

472

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00746

ESP6500AA

AF:

0.0234

AC:

103

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00222

AC:

269

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

.;T;.;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.72

T;T;T;T

MetaRNN

Benign

0.0036

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

.;N;D;.

REVEL

Benign

0.027

Sift

Uncertain

0.0090

.;D;D;.

Sift4G

Uncertain

0.020

D;D;D;D

Polyphen

0.58, 0.71

.;P;P;.

Vest4

0.26

MVP

0.15

MPC

0.27

ClinPred

0.020

GERP RS

-2.7

Varity_R

0.43

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000046

dbscSNV1_RF

Benign

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over