6-41276188-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.277

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]

ACMG classification

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	UniProt
TREM1	NM_018643.5	c.642C>G	p.Phe214Leu	missense_variant	4/4	ENST00000244709.9
TREM1	NM_001242590.3	c.449C>G	p.Ser150Cys	missense_variant	3/3
TREM1	XM_011514696.3	c.599+4773C>G		intron_variant
TREM1	NR_136332.2	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	c.642C>G	p.Phe214Leu	missense_variant	4/4	1	NM_018643.5	P2
TREM1	ENST00000334475.10	c.449C>G	p.Ser150Cys	missense_variant	3/3	1		A2
TREM1	ENST00000589614.5	c.599+4773C>G		intron_variant		2		A2
TREM1	ENST00000589695.1	n.317C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3290 AN: 152036 Hom.: 112 Cov.: 32

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.: 46 AF XY: 0.00466 AC XY: 633 AN XY: 135876

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.: 31 AF XY: 0.00221 AC XY: 1610 AN XY: 727238

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.: 32 AF XY: 0.0211 AC XY: 1571 AN XY: 74394

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.: 6

Bravo AF: 0.0248

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0679 AC: 299

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00694 AC: 842

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.7
Dann	Uncertain	0.98
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.013
MutPred		0.18		Loss of sheet (P = 0.0315);
MVP		0.11
MPC		0.12
ClinPred		0.0051	T
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

Other links and lift over

dbSNP: rs2234245; hg19: chr6-41243926;