6-41194780-T-C

Variant names:

• chr6-41194780-T-C
• rs3747742
• NM_024807.4:c.430A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024807.4(TREML2):​c.430A>G​(p.Ser144Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,607,176 control chromosomes in the GnomAD database, including 76,242 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S144C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.30 (6835 hom., cov: 31)
  • Exomes 𝑓: 0.31 (69407 hom.)
• Consequence: TREML2 NM_024807.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 62 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.7291646E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024807.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREML2	NM_024807.4	MANE Select	c.430A>G	p.Ser144Gly	missense	Exon 3 of 5	NP_079083.2	Q5T2D2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREML2	ENST00000483722.2	TSL:1 MANE Select	c.430A>G	p.Ser144Gly	missense	Exon 3 of 5	ENSP00000418767.1	Q5T2D2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45008 AN: 151894 Hom.: 6834 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.289

GnomAD2 exomes AF: 0.331 AC: 81103 AN: 244868 AF XY: 0.328

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.360

Gnomad FIN exome AF: 0.387

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.306 AC: 445651 AN: 1455164 Hom.: 69407 Cov.: 36 AF XY: 0.307 AC XY: 222119 AN XY: 723488

African (AFR) AF: 0.225 AC: 7499 AN: 33278

American (AMR) AF: 0.437 AC: 19105 AN: 43752

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 7047 AN: 25552

East Asian (EAS) AF: 0.335 AC: 13260 AN: 39636

South Asian (SAS) AF: 0.331 AC: 28209 AN: 85230

European-Finnish (FIN) AF: 0.382 AC: 20351 AN: 53232

Middle Eastern (MID) AF: 0.262 AC: 1500 AN: 5726

European-Non Finnish (NFE) AF: 0.298 AC: 330246 AN: 1108678

Other (OTH) AF: 0.307 AC: 18434 AN: 60080

GnomAD4 genome AF: 0.296 AC: 45036 AN: 152012 Hom.: 6835 Cov.: 31 AF XY: 0.302 AC XY: 22443 AN XY: 74264

African (AFR) AF: 0.229 AC: 9505 AN: 41478

American (AMR) AF: 0.367 AC: 5603 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 962 AN: 3464

East Asian (EAS) AF: 0.352 AC: 1813 AN: 5148

South Asian (SAS) AF: 0.337 AC: 1621 AN: 4812

European-Finnish (FIN) AF: 0.375 AC: 3955 AN: 10556

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20568 AN: 67950

Other (OTH) AF: 0.287 AC: 607 AN: 2112

Alfa AF: 0.302 Hom.: 33017

Bravo AF: 0.294

TwinsUK AF: 0.296 AC: 1096

ALSPAC AF: 0.291 AC: 1123

ESP6500AA AF: 0.226 AC: 996

ESP6500EA AF: 0.304 AC: 2618

ExAC AF: 0.321 AC: 38967

Asia WGS AF: 0.377 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.6
DANN	Benign	0.94
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.00037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.40
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.032
Sift	Benign	0.22	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.013
MPC		0.21
ClinPred		0.0038	T
GERP RS		-2.2
Varity_R		0.036
gMVP		0.35
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3747742; hg19: chr6-41162518; COSMIC: COSV72439043;