6-41194780-T-C

Position:

• chr6-41194780-T-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREML2	NM_024807.4	c.430A>G	p.Ser144Gly	missense_variant	3/5	ENST00000483722.2	NP_079083.2
TREML2	XM_011514917.3	c.109A>G	p.Ser37Gly	missense_variant	2/4		XP_011513219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREML2	ENST00000483722.2	c.430A>G	p.Ser144Gly	missense_variant	3/5	1	NM_024807.4	ENSP00000418767.1

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

GnomAD3 exomes AF: 0.331 AC: 81103 AN: 244868 Hom.: 14029 AF XY: 0.328 AC XY: 43328 AN XY: 132296

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 SAS exome AF: 0.335

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

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.307

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

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.287

Alfa AF: 0.303 Hom.: 18114

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 v4.3

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
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

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