Genetic Variant TREM1:c.*123G>A (chr6-41276002-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Publications

47 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TREM1	NM_018643.5	MANE Select	c.*123G>A	3_prime_UTR	Exon 4 of 4	NP_061113.1
TREM1	NM_001242590.3		c.*182G>A	3_prime_UTR	Exon 3 of 3	NP_001229519.1
TREM1	NR_136332.2		n.855G>A	non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TREM1	ENST00000244709.9	TSL:1 MANE Select	c.*123G>A	3_prime_UTR	Exon 4 of 4	ENSP00000244709.3
TREM1	ENST00000334475.11	TSL:1	c.*182G>A	3_prime_UTR	Exon 3 of 3	ENSP00000334284.5
TREM1	ENST00000589614.6	TSL:2	c.599+4959G>A	intron	N/A	ENSP00000465688.1

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66300

AN:

151822

Hom.:

14938

Cov.:

show subpopulations

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.:

AF XY:

0.448

AC XY:

130273

AN XY:

290844

show subpopulations

African (AFR)

AF:

0.348

AC:

5260

AN:

15110

American (AMR)

AF:

0.498

AC:

14049

AN:

28212

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

6975

AN:

15962

East Asian (EAS)

AF:

0.316

AC:

10231

AN:

32378

South Asian (SAS)

AF:

0.333

AC:

17991

AN:

53988

European-Finnish (FIN)

AF:

0.424

AC:

18705

AN:

44118

Middle Eastern (MID)

AF:

0.524

AC:

1764

AN:

3366

European-Non Finnish (NFE)

AF:

0.492

AC:

161657

AN:

328672

Other (OTH)

AF:

0.456

AC:

13586

AN:

29770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6467

12935

19402

25870

32337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1462

2924

4386

5848

7310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.437

AC:

66345

AN:

151940

Hom.:

14950

Cov.:

AF XY:

0.433

AC XY:

32163

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.356

AC:

14738

AN:

41418

American (AMR)

AF:

0.507

AC:

7751

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1520

AN:

3468

East Asian (EAS)

AF:

0.258

AC:

1335

AN:

5166

South Asian (SAS)

AF:

0.304

AC:

1465

AN:

4812

European-Finnish (FIN)

AF:

0.419

AC:

4424

AN:

10546

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.494

AC:

33596

AN:

67940

Other (OTH)

AF:

0.465

AC:

982

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1904

3808

5711

7615

9519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.473

Hom.:

47932

Bravo

AF:

0.443

Asia WGS

AF:

0.251

AC:

871

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.8

(source)

DANN

Benign

0.49

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over