4-153204846-T-C

Position:

• chr4-153204846-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015271.5(TRIM2):​c.30+286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,074 control chromosomes in the GnomAD database, including 3,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.18 (3788 hom., cov: 32)
• Consequence: TRIM2 NM_015271.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-153204846-T-C is Benign according to our data. Variant chr4-153204846-T-C is described in ClinVar as [Benign]. Clinvar id is 1264712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM2	NM_015271.5	c.30+286T>C		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+286T>C		intron_variant		1	NM_015271.5	ENSP00000339659

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26828 AN: 151956 Hom.: 3782 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.0913

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.177 AC: 26872 AN: 152074 Hom.: 3788 Cov.: 32 AF XY: 0.174 AC XY: 12972 AN XY: 74352

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.0742

Gnomad4 SAS AF: 0.0849

Gnomad4 FIN AF: 0.0913

Gnomad4 NFE AF: 0.0820

Gnomad4 OTH AF: 0.162

Alfa AF: 0.102 Hom.: 1703

Bravo AF: 0.194

Asia WGS AF: 0.110 AC: 384 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.37
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10019436; hg19: chr4-154125998;