chr6-41160234-A-G

Variant names:

• chr6-41160234-A-G
• rs7748513
• NM_018965.4:c.392-352T>C

Variant summary

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

The NM_018965.4(TREM2):​c.392-352T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,148 control chromosomes in the GnomAD database, including 4,719 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 0.16 (4719 hom., cov: 32)
• Consequence: TREM2 NM_018965.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• Publications: 25 publications found

Genes affected

TREM2 (HGNC:17761): (triggering receptor expressed on myeloid cells 2) This gene encodes a membrane protein that forms a receptor signaling complex with the TYRO protein tyrosine kinase binding protein. The encoded protein functions in immune response and may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in this gene are a cause of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

TREM2 Gene-Disease associations (from GenCC):

• polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000290034 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018965.4. 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
	TREM2	NM_018965.4	MANE Select	c.392-352T>C		intron	N/A	NP_061838.1	Q5TCX1
	TREM2	NM_001271821.2		c.392-352T>C		intron	N/A	NP_001258750.1	Q9NZC2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREM2	ENST00000373113.8	TSL:1 MANE Select	c.392-352T>C		intron	N/A	ENSP00000362205.3	Q9NZC2-1
	TREM2	ENST00000373122.8	TSL:1	c.392-352T>C		intron	N/A	ENSP00000362214.4	Q9NZC2-3
	TREM2	ENST00000338469.3	TSL:1	c.392-352T>C		intron	N/A	ENSP00000342651.4	Q9NZC2-2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24009 AN: 152030 Hom.: 4702 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.00694

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 24069 AN: 152148 Hom.: 4719 Cov.: 32 AF XY: 0.153 AC XY: 11415 AN XY: 74400

African (AFR) AF: 0.463 AC: 19188 AN: 41440

American (AMR) AF: 0.0912 AC: 1396 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 217 AN: 3468

East Asian (EAS) AF: 0.00696 AC: 36 AN: 5176

South Asian (SAS) AF: 0.0663 AC: 320 AN: 4826

European-Finnish (FIN) AF: 0.0219 AC: 232 AN: 10612

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0347 AC: 2357 AN: 68008

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.0829 Hom.: 4831

Bravo AF: 0.177

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.029
DANN	Benign	0.28
PhyloP100		-0.97
Mutation Taster		=100/0	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: rs7748513; hg19: chr6-41127972;