6-41278735-T-C

Variant names:

• chr6-41278735-T-C
• rs4711668
• NM_018643.5:c.599+2226A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018643.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREM1	NM_018643.5	MANE Select	c.599+2226A>G		intron	N/A	NP_061113.1
	TREM1	NM_001242590.3		c.407-2505A>G		intron	N/A	NP_001229519.1
	TREM1	NR_136332.2		n.626+2226A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREM1	ENST00000244709.9	TSL:1 MANE Select	c.599+2226A>G		intron	N/A	ENSP00000244709.3
	TREM1	ENST00000334475.11	TSL:1	c.407-2505A>G		intron	N/A	ENSP00000334284.5
	TREM1	ENST00000589614.6	TSL:2	c.599+2226A>G		intron	N/A	ENSP00000465688.1

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

African (AFR) AF: 0.885 AC: 36722 AN: 41484

American (AMR) AF: 0.745 AC: 11381 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2303 AN: 3472

East Asian (EAS) AF: 0.542 AC: 2785 AN: 5136

South Asian (SAS) AF: 0.558 AC: 2682 AN: 4810

European-Finnish (FIN) AF: 0.588 AC: 6169 AN: 10500

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46570 AN: 67988

Other (OTH) AF: 0.741 AC: 1561 AN: 2106

Alfa AF: 0.698 Hom.: 162527

Bravo AF: 0.753

Asia WGS AF: 0.537 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.0
DANN	Benign	0.77
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4711668; hg19: chr6-41246473;