NM_018643.5:c.600-599G>C

Variant names:

• chr6-41276829-C-G
• rs1817537
• NM_018643.5:c.600-599G>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.600-599G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,728 control chromosomes in the GnomAD database, including 15,228 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 0.44 (15228 hom., cov: 30)
• Consequence: TREM1 NM_018643.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64
• Publications: 14 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREM1	NM_018643.5	c.600-599G>C		intron_variant	Intron 3 of 3	ENST00000244709.9	NP_061113.1
TREM1	NM_001242590.3	c.407-599G>C		intron_variant	Intron 2 of 2		NP_001229519.1
TREM1	NR_136332.2	n.627-599G>C		intron_variant	Intron 3 of 4
TREM1	XM_011514696.3	c.599+4132G>C		intron_variant	Intron 3 of 3		XP_011512998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREM1	ENST00000244709.9	c.600-599G>C		intron_variant	Intron 3 of 3	1	NM_018643.5	ENSP00000244709.3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67124 AN: 151610 Hom.: 15210 Cov.: 30

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.443 AC: 67174 AN: 151728 Hom.: 15228 Cov.: 30 AF XY: 0.439 AC XY: 32520 AN XY: 74138

African (AFR) AF: 0.377 AC: 15591 AN: 41304

American (AMR) AF: 0.509 AC: 7763 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1329 AN: 5146

South Asian (SAS) AF: 0.300 AC: 1447 AN: 4818

European-Finnish (FIN) AF: 0.418 AC: 4392 AN: 10510

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33644 AN: 67914

Other (OTH) AF: 0.463 AC: 974 AN: 2104

Alfa AF: 0.457 Hom.: 1940

Bravo AF: 0.450

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.033
DANN	Benign	0.34
PhyloP100		-3.6
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: rs1817537; hg19: chr6-41244567; COSMIC: COSV55149362; COSMIC: COSV55149362;