6-41281014-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_018643.5(TREM1):c.546T>C(p.Asp182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,614,244 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (25 hom.)
• Consequence: TREM1 NM_018643.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-41281014-A-G is Benign according to our data. Variant chr6-41281014-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.233 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00209 (3054/1461894) while in subpopulation MID AF= 0.0187 (108/5768). AF 95% confidence interval is 0.0159. There are 25 homozygotes in gnomad4_exome. There are 1545 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREM1	NM_018643.5	c.546T>C	p.Asp182=	synonymous_variant	3/4	ENST00000244709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREM1	ENST00000244709.9	c.546T>C	p.Asp182=	synonymous_variant	3/4	1	NM_018643.5	P2

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 575 AN: 152232 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00591

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00307 AC: 772 AN: 251460 Hom.: 11 AF XY: 0.00311 AC XY: 423 AN XY: 135906

Gnomad AFR exome AF: 0.00732

Gnomad AMR exome AF: 0.00390

Gnomad ASJ exome AF: 0.0276

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00172

Gnomad OTH exome AF: 0.00521

GnomAD4 exome AF: 0.00209 AC: 3054 AN: 1461894 Hom.: 25 Cov.: 32 AF XY: 0.00212 AC XY: 1545 AN XY: 727248

Gnomad4 AFR exome AF: 0.00947

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.0285

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.00123

Gnomad4 OTH exome AF: 0.00495

GnomAD4 genome AF: 0.00378 AC: 576 AN: 152350 Hom.: 5 Cov.: 32 AF XY: 0.00384 AC XY: 286 AN XY: 74502

Gnomad4 AFR AF: 0.00594

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00429 Hom.: 4

Bravo AF: 0.00437

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00279

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, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.57
Dann	Benign	0.31

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: rs2234240; hg19: chr6-41248752;