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GeneBe

6-41198139-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_024807.4(TREML2):c.346T>C(p.Leu116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000929 in 1,604,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00094 ( 0 hom. )

Consequence

TREML2
NM_024807.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.00
Variant links:
Genes affected
TREML2 (HGNC:21092): (triggering receptor expressed on myeloid cells like 2) TREML2 is located in a gene cluster on chromosome 6 with the single Ig variable (IgV) domain activating receptors TREM1 (MIM 605085) and TREM2 (MIM 605086), but it has distinct structural and functional properties (Allcock et al., 2003 [PubMed 12645956]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-41198139-A-G is Benign according to our data. Variant chr6-41198139-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656541.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TREML2NM_024807.4 linkuse as main transcriptc.346T>C p.Leu116= synonymous_variant 2/5 ENST00000483722.2
TREML2XM_011514917.3 linkuse as main transcriptc.55+2815T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TREML2ENST00000483722.2 linkuse as main transcriptc.346T>C p.Leu116= synonymous_variant 2/51 NM_024807.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000808
AC:
123
AN:
152186
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000850
Gnomad ASJ
AF:
0.00749
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000970
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00131
AC:
324
AN:
247902
Hom.:
0
AF XY:
0.00126
AC XY:
169
AN XY:
134052
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000465
Gnomad ASJ exome
AF:
0.00969
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00168
Gnomad FIN exome
AF:
0.000419
Gnomad NFE exome
AF:
0.00127
Gnomad OTH exome
AF:
0.00165
GnomAD4 exome
AF:
0.000942
AC:
1368
AN:
1452032
Hom.:
0
Cov.:
33
AF XY:
0.000961
AC XY:
692
AN XY:
720244
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.000495
Gnomad4 ASJ exome
AF:
0.00950
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00152
Gnomad4 FIN exome
AF:
0.000394
Gnomad4 NFE exome
AF:
0.000783
Gnomad4 OTH exome
AF:
0.00115
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000808
AC:
123
AN:
152304
Hom.:
0
Cov.:
33
AF XY:
0.000765
AC XY:
57
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000849
Gnomad4 ASJ
AF:
0.00749
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00186
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000971
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00169
Hom.:
0
Bravo
AF:
0.000820
EpiCase
AF:
0.000927
EpiControl
AF:
0.00119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2022TREML2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
Cadd
Benign
0.30
Dann
Benign
0.36

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140974034; hg19: chr6-41165877; API