6-41277434-C-T

Position:

• chr6-41277434-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREM1	NM_018643.5	c.600-1204G>A		intron_variant		ENST00000244709.9
TREM1	NM_001242590.3	c.407-1204G>A		intron_variant
TREM1	XM_011514696.3	c.599+3527G>A		intron_variant
TREM1	NR_136332.2	n.627-1204G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREM1	ENST00000244709.9	c.600-1204G>A		intron_variant		1	NM_018643.5	P2
TREM1	ENST00000334475.10	c.407-1204G>A		intron_variant		1		A2
TREM1	ENST00000589614.5	c.599+3527G>A		intron_variant		2		A2
TREM1	ENST00000589695.1	n.275-1204G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.460

Alfa AF: 0.322 Hom.: 772

Bravo AF: 0.442

Asia WGS AF: 0.249 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.92
DANN	Benign	0.39

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: rs3804277; hg19: chr6-41245172;