chr4-153270118-C-T

Position:

• chr4-153270118-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015271.5(TRIM2):​c.31-217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 151,724 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.025 (94 hom., cov: 31)
• Consequence: TRIM2 NM_015271.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.490

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-153270118-C-T is Benign according to our data. Variant chr4-153270118-C-T is described in ClinVar as [Benign]. Clinvar id is 1279594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM2	NM_015271.5	c.31-217C>T		intron_variant		ENST00000338700.10	NP_056086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM2	ENST00000338700.10	c.31-217C>T		intron_variant		1	NM_015271.5	ENSP00000339659

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3800 AN: 151606 Hom.: 94 Cov.: 31

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0263

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000833

Gnomad FIN AF: 0.00161

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00905

Gnomad OTH AF: 0.0265

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

GnomAD4 genome AF: 0.0251 AC: 3809 AN: 151724 Hom.: 94 Cov.: 31 AF XY: 0.0236 AC XY: 1753 AN XY: 74154

Gnomad4 AFR AF: 0.0677

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.0263

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000834

Gnomad4 FIN AF: 0.00161

Gnomad4 NFE AF: 0.00906

Gnomad4 OTH AF: 0.0262

Alfa AF: 0.0192 Hom.: 8

Bravo AF: 0.0283

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.2
DANN	Benign	0.69

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: rs6535912; hg19: chr4-154191270;