chr6-41286177-A-G

Variant names:

• chr6-41286177-A-G
• rs3789205
• NM_018643.5:c.49+430T>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.49+430T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,230 control chromosomes in the GnomAD database, including 890 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 0.097 (890 hom., cov: 32)
• Consequence: TREM1 NM_018643.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREM1	NM_018643.5	c.49+430T>C		intron_variant	Intron 1 of 3	ENST00000244709.9	NP_061113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREM1	ENST00000244709.9	c.49+430T>C		intron_variant	Intron 1 of 3	1	NM_018643.5	ENSP00000244709.3

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14770 AN: 152112 Hom.: 884 Cov.: 32

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.0982

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

GnomAD4 genome AF: 0.0971 AC: 14784 AN: 152230 Hom.: 890 Cov.: 32 AF XY: 0.101 AC XY: 7481 AN XY: 74420

African (AFR) AF: 0.0586 AC: 2435 AN: 41548

American (AMR) AF: 0.122 AC: 1865 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0773 AC: 268 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1587 AN: 5164

South Asian (SAS) AF: 0.130 AC: 625 AN: 4826

European-Finnish (FIN) AF: 0.122 AC: 1293 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0939 AC: 6390 AN: 68016

Other (OTH) AF: 0.105 AC: 222 AN: 2110

Alfa AF: 0.102 Hom.: 94

Bravo AF: 0.0977

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.9
DANN	Benign	0.80
PhyloP100		0.61
PromoterAI		0.00090	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3789205; hg19: chr6-41253915;