6-41278895-A-G

Variant names:

• chr6-41278895-A-G
• rs6910730
• NM_018643.5:c.599+2066T>C

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+2066T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,046 control chromosomes in the GnomAD database, including 4,640 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 0.21 (4640 hom., cov: 32)
• Consequence: TREM1 NM_018643.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 31 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 = 0.408 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREM1	NM_018643.5	MANE Select	c.599+2066T>C		intron	N/A	NP_061113.1	Q38L15
	TREM1	NM_001242590.3		c.407-2665T>C		intron	N/A	NP_001229519.1	Q9NP99-2
	TREM1	NR_136332.2		n.626+2066T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREM1	ENST00000244709.9	TSL:1 MANE Select	c.599+2066T>C		intron	N/A	ENSP00000244709.3	Q9NP99-1
	TREM1	ENST00000334475.11	TSL:1	c.407-2665T>C		intron	N/A	ENSP00000334284.5	Q9NP99-2
	TREM1	ENST00000589614.6	TSL:2	c.599+2066T>C		intron	N/A	ENSP00000465688.1	K7EKM5

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31517 AN: 151928 Hom.: 4627 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.208 AC: 31567 AN: 152046 Hom.: 4640 Cov.: 32 AF XY: 0.207 AC XY: 15403 AN XY: 74340

African (AFR) AF: 0.413 AC: 17117 AN: 41410

American (AMR) AF: 0.162 AC: 2476 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 522 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1445 AN: 5150

South Asian (SAS) AF: 0.231 AC: 1114 AN: 4822

European-Finnish (FIN) AF: 0.106 AC: 1123 AN: 10620

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7154 AN: 67966

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.131 Hom.: 1360

Bravo AF: 0.220

Asia WGS AF: 0.267 AC: 928 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	3.1
DANN	Benign	0.27
PhyloP100		-0.50
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: rs6910730; hg19: chr6-41246633;