chr6-41276002-C-T

Position:

• chr6-41276002-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.*123G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 703,516 control chromosomes in the GnomAD database, including 73,439 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 (14950 hom., cov: 31)
  • Exomes 𝑓: 0.45 (58489 hom.)
• Consequence: TREM1 NM_018643.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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]

TREM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREM1	NM_018643.5	c.*123G>A		3_prime_UTR_variant	4/4	ENST00000244709.9	NP_061113.1
TREM1	NM_001242590.3	c.*182G>A		3_prime_UTR_variant	3/3		NP_001229519.1
TREM1	XM_011514696.3	c.599+4959G>A		intron_variant			XP_011512998.1
TREM1	NR_136332.2	n.855G>A		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREM1	ENST00000244709	c.*123G>A		3_prime_UTR_variant	4/4	1	NM_018643.5	ENSP00000244709.3
TREM1	ENST00000334475.10	c.*182G>A		3_prime_UTR_variant	3/3	1		ENSP00000334284.5
TREM1	ENST00000589614.5	c.599+4959G>A		intron_variant		2		ENSP00000465688.1
TREM1	ENST00000589695.1	n.503G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66300 AN: 151822 Hom.: 14938 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.454 AC: 250218 AN: 551576 Hom.: 58489 Cov.: 7 AF XY: 0.448 AC XY: 130273 AN XY: 290844

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.456

GnomAD4 genome AF: 0.437 AC: 66345 AN: 151940 Hom.: 14950 Cov.: 31 AF XY: 0.433 AC XY: 32163 AN XY: 74240

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.465

Alfa AF: 0.481 Hom.: 30899

Bravo AF: 0.443

Asia WGS AF: 0.251 AC: 871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.49

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: rs2234246; hg19: chr6-41243740; COSMIC: COSV55149987; COSMIC: COSV55149987;