rs12644284

Positions:

• chr4-153232848-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015271.5(TRIM2):​c.30+28288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,086 control chromosomes in the GnomAD database, including 3,222 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 0.18 (3222 hom., cov: 32)
• Consequence: TRIM2 NM_015271.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM2	NM_015271.5	c.30+28288A>G		intron_variant		ENST00000338700.10	NP_056086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM2	ENST00000338700.10	c.30+28288A>G		intron_variant		1	NM_015271.5	ENSP00000339659

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27851 AN: 151968 Hom.: 3221 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.183 AC: 27854 AN: 152086 Hom.: 3222 Cov.: 32 AF XY: 0.179 AC XY: 13277 AN XY: 74336

Gnomad4 AFR AF: 0.0480

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.191

Alfa AF: 0.250 Hom.: 9030

Bravo AF: 0.176

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.60

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: rs12644284; hg19: chr4-154154000;