rs7748513

Positions:

• chr6-41160234-A-G
• chr6-41160234-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREM2	NM_018965.4	c.392-352T>C		intron_variant		ENST00000373113.8	NP_061838.1
TREM2	NM_001271821.2	c.392-352T>C		intron_variant			NP_001258750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREM2	ENST00000373113.8	c.392-352T>C		intron_variant		1	NM_018965.4	ENSP00000362205	P1
TREM2	ENST00000338469.3	c.392-352T>C		intron_variant		1		ENSP00000342651
TREM2	ENST00000373122.8	c.392-352T>C		intron_variant		1		ENSP00000362214
	ENST00000702590.1	n.364+4671A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.0626

Gnomad4 EAS AF: 0.00696

Gnomad4 SAS AF: 0.0663

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0547 Hom.: 690

Bravo AF: 0.177

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.029
DANN	Benign	0.28

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: rs7748513; hg19: chr6-41127972;