rs4696443

Variant names:

• chr4-153230836-A-G
• rs4696443
• NM_015271.5:c.30+26276A>G

Variant summary

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

The NM_015271.5(TRIM2):​c.30+26276A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,150 control chromosomes in the GnomAD database, including 5,853 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 0.23 (5853 hom., cov: 33)
• Consequence: TRIM2 NM_015271.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 6 publications found

Genes affected

TRIM2 (HGNC:15974): (tripartite motif containing 2) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic filaments. It plays a neuroprotective role and functions as an E3-ubiquitin ligase in proteasome-mediated degradation of target proteins. Mutations in this gene can cause early-onset axonal neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

TRIM2 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 2R

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000288637 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015271.5. 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
	TRIM2	NM_015271.5	MANE Select	c.30+26276A>G		intron	N/A	NP_056086.2	Q9C040-2
	TRIM2	NM_001375488.1		c.30+26276A>G		intron	N/A	NP_001362417.1
	TRIM2	NM_001375489.1		c.30+26276A>G		intron	N/A	NP_001362418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM2	ENST00000338700.10	TSL:1 MANE Select	c.30+26276A>G		intron	N/A	ENSP00000339659.5	Q9C040-2
	ENSG00000288637	ENST00000675838.1		c.-52+26276A>G		intron	N/A	ENSP00000501593.1	A0A6Q8PF18
	TRIM2	ENST00000437508.7	TSL:1	c.-48-39502A>G		intron	N/A	ENSP00000415812.2	Q9C040-1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34924 AN: 152032 Hom.: 5838 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.0928

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.230 AC: 34986 AN: 152150 Hom.: 5853 Cov.: 33 AF XY: 0.224 AC XY: 16678 AN XY: 74414

African (AFR) AF: 0.469 AC: 19435 AN: 41466

American (AMR) AF: 0.220 AC: 3356 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3468

East Asian (EAS) AF: 0.0927 AC: 480 AN: 5180

South Asian (SAS) AF: 0.0927 AC: 447 AN: 4824

European-Finnish (FIN) AF: 0.0943 AC: 1000 AN: 10604

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9059 AN: 68004

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.162 Hom.: 4431

Bravo AF: 0.248

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		1.3
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: rs4696443; hg19: chr4-154151988;