rs6910730

Positions:

• chr6-41278895-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000244709.9(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 ENST00000244709.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREM1	NM_018643.5	c.599+2066T>C		intron_variant		ENST00000244709.9	NP_061113.1
TREM1	NM_001242590.3	c.407-2665T>C		intron_variant			NP_001229519.1
TREM1	XM_011514696.3	c.599+2066T>C		intron_variant			XP_011512998.1
TREM1	NR_136332.2	n.626+2066T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREM1	ENST00000244709.9	c.599+2066T>C		intron_variant		1	NM_018643.5	ENSP00000244709	P2
TREM1	ENST00000334475.10	c.407-2665T>C		intron_variant		1		ENSP00000334284	A2
TREM1	ENST00000589614.5	c.599+2066T>C		intron_variant		2		ENSP00000465688	A2
TREM1	ENST00000589695.1	n.274+2066T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.201

Alfa AF: 0.136 Hom.: 1015

Bravo AF: 0.220

Asia WGS AF: 0.267 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.1
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs6910730; hg19: chr6-41246633;