Variant 6-41276188-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018643.5(TREM1):c.642C>G(p.Phe214Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,614,018 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. 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 0.022 ( 113 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 118 hom. )

Consequence

TREM1
NM_018643.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.277

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=0.00379017).

BP6

Variant 6-41276188-G-C is Benign according to our data. Variant chr6-41276188-G-C is described in ClinVar as [Benign]. Clinvar id is 768088.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TREM1	NM_018643.5 linkuse as main transcript	c.642C>G	p.Phe214Leu	missense_variant	4/4	ENST00000244709.9
TREM1	NM_001242590.3 linkuse as main transcript	c.449C>G	p.Ser150Cys	missense_variant	3/3
TREM1	XM_011514696.3 linkuse as main transcript	c.599+4773C>G		intron_variant
TREM1	NR_136332.2 linkuse as main transcript	n.669C>G		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREM1	ENST00000244709.9 linkuse as main transcript	c.642C>G	p.Phe214Leu	missense_variant	4/4	1	NM_018643.5	P2	Q9NP99-1
TREM1	ENST00000334475.10 linkuse as main transcript	c.449C>G	p.Ser150Cys	missense_variant	3/3	1		A2	Q9NP99-2
TREM1	ENST00000589614.5 linkuse as main transcript	c.599+4773C>G		intron_variant		2		A2
TREM1	ENST00000589695.1 linkuse as main transcript	n.317C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3290

AN:

152036

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0731

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00601

AC:

1510

AN:

251428

Hom.:

AF XY:

0.00466

AC XY:

633

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0727

Gnomad AMR exome

AF:

0.00682

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000519

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00251

AC:

3667

AN:

1461864

Hom.:

118

Cov.:

AF XY:

0.00221

AC XY:

1610

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0750

Gnomad4 AMR exome

AF:

0.00740

Gnomad4 ASJ exome

AF:

0.000803

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000382

Gnomad4 OTH exome

AF:

0.00555

GnomAD4 genome

AF:

0.0216

AC:

3294

AN:

152154

Hom.:

113

Cov.:

AF XY:

0.0211

AC XY:

1571

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0730

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.0248

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0679

AC:

299

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00694

AC:

842

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000830

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

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.7

DANN

Uncertain

0.98

DEOGEN2

Benign

0.060

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

1.3

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.013

MutPred

0.18

Loss of sheet (P = 0.0315);

MVP

0.11

MPC

0.12

ClinPred

0.0051

GERP RS

1.0

Varity_R

0.032

gMVP

0.095

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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