6-41277434-C-T

Variant names:

• chr6-41277434-C-T
• rs3804277
• NM_018643.5:c.600-1204G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018643.5(TREM1):​c.600-1204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,896 control chromosomes in the GnomAD database, including 14,930 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 (14930 hom., cov: 31)
• Consequence: TREM1 NM_018643.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.496 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.600-1204G>A		intron	N/A	NP_061113.1	Q38L15
	TREM1	NM_001242590.3		c.407-1204G>A		intron	N/A	NP_001229519.1	Q9NP99-2
	TREM1	NR_136332.2		n.627-1204G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREM1	ENST00000244709.9	TSL:1 MANE Select	c.600-1204G>A		intron	N/A	ENSP00000244709.3	Q9NP99-1
	TREM1	ENST00000334475.11	TSL:1	c.407-1204G>A		intron	N/A	ENSP00000334284.5	Q9NP99-2
	TREM1	ENST00000589614.6	TSL:2	c.599+3527G>A		intron	N/A	ENSP00000465688.1	K7EKM5

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66238 AN: 151780 Hom.: 14919 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.436 AC: 66279 AN: 151896 Hom.: 14930 Cov.: 31 AF XY: 0.432 AC XY: 32080 AN XY: 74210

African (AFR) AF: 0.355 AC: 14700 AN: 41388

American (AMR) AF: 0.506 AC: 7720 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1343 AN: 5174

South Asian (SAS) AF: 0.300 AC: 1446 AN: 4822

European-Finnish (FIN) AF: 0.418 AC: 4401 AN: 10536

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33666 AN: 67930

Other (OTH) AF: 0.460 AC: 969 AN: 2108

Alfa AF: 0.324 Hom.: 817

Bravo AF: 0.442

Asia WGS AF: 0.249 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.92
DANN	Benign	0.39
PhyloP100		-0.72
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: rs3804277; hg19: chr6-41245172;