4-153270074-G-A

Position:

• chr4-153270074-G-A

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.31-261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 151,962 control chromosomes in the GnomAD database, including 1,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1186 hom., cov: 31)
• Consequence: TRIM2 NM_015271.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.77

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=-1.03).
• BP6: Variant 4-153270074-G-A is Benign according to our data. Variant chr4-153270074-G-A is described in ClinVar as [Benign]. Clinvar id is 1263048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM2	NM_015271.5	c.31-261G>A		intron_variant		ENST00000338700.10	NP_056086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM2	ENST00000338700.10	c.31-261G>A		intron_variant		1	NM_015271.5	ENSP00000339659

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17027 AN: 151846 Hom.: 1187 Cov.: 31

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.0811

Gnomad EAS AF: 0.0347

Gnomad SAS AF: 0.0932

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.112 AC: 17024 AN: 151962 Hom.: 1186 Cov.: 31 AF XY: 0.110 AC XY: 8200 AN XY: 74260

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.0811

Gnomad4 EAS AF: 0.0344

Gnomad4 SAS AF: 0.0935

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0921 Hom.: 183

Bravo AF: 0.0976

Asia WGS AF: 0.0840 AC: 294 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 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.31

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: rs41280463; hg19: chr4-154191226;