6-41282585-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_018643.5(TREM1):c.216G>A(p.Arg72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000363 in 1,614,166 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: TREM1 NM_018643.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.76

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-41282585-C-T is Benign according to our data. Variant chr6-41282585-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.76 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREM1	NM_018643.5	c.216G>A	p.Arg72=	synonymous_variant	2/4	ENST00000244709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREM1	ENST00000244709.9	c.216G>A	p.Arg72=	synonymous_variant	2/4	1	NM_018643.5	P2

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 114 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000402 AC: 101 AN: 251388 Hom.: 0 AF XY: 0.000346 AC XY: 47 AN XY: 135880

Gnomad AFR exome AF: 0.00203

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000325

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000322 AC: 471 AN: 1461892 Hom.: 1 Cov.: 31 AF XY: 0.000296 AC XY: 215 AN XY: 727246

Gnomad4 AFR exome AF: 0.00275

Gnomad4 AMR exome AF: 0.000648

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000260

Gnomad4 OTH exome AF: 0.000662

GnomAD4 genome AF: 0.000755 AC: 115 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 63 AN XY: 74462

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000523 Hom.: 0

Bravo AF: 0.000812

EpiCase AF: 0.000436

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

TREM1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.54
Dann	Benign	0.42

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: rs2234238; hg19: chr6-41250323;