6-41278735-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018643.5(TREM1):c.599+2226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 151,982 control chromosomes in the GnomAD database, including 41,393 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (41393 hom., cov: 31)
• Consequence: TREM1 NM_018643.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREM1	NM_018643.5	c.599+2226A>G		intron_variant		ENST00000244709.9
TREM1	NM_001242590.3	c.407-2505A>G		intron_variant
TREM1	XM_011514696.3	c.599+2226A>G		intron_variant
TREM1	NR_136332.2	n.626+2226A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREM1	ENST00000244709.9	c.599+2226A>G		intron_variant		1	NM_018643.5	P2
TREM1	ENST00000334475.10	c.407-2505A>G		intron_variant		1		A2
TREM1	ENST00000589614.5	c.599+2226A>G		intron_variant		2		A2
TREM1	ENST00000589695.1	n.274+2226A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110934 AN: 151866 Hom.: 41342 Cov.: 31

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.739

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.731 AC: 111041 AN: 151982 Hom.: 41393 Cov.: 31 AF XY: 0.723 AC XY: 53685 AN XY: 74246

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.741

Alfa AF: 0.691 Hom.: 80203

Bravo AF: 0.753

Asia WGS AF: 0.537 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	5.0
Dann	Benign	0.77

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: rs4711668; hg19: chr6-41246473;