chr4-153204283-T-C

Position:

• chr4-153204283-T-C

Variant summary

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

The ENST00000437508.7(TRIM2):​c.-49+51013T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,106 control chromosomes in the GnomAD database, including 18,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.43 (18248 hom., cov: 32)
• Consequence: TRIM2 ENST00000437508.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.65

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=-0.83).
• BP6: Variant 4-153204283-T-C is Benign according to our data. Variant chr4-153204283-T-C is described in ClinVar as [Benign]. Clinvar id is 1250955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM2	NM_001130067.2	c.-49+51013T>C		intron_variant			NP_001123539.1
TRIM2	NM_001351056.2	c.-49+51671T>C		intron_variant			NP_001337985.1
TRIM2	NM_001375513.1	c.-49+51671T>C		intron_variant			NP_001362442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM2	ENST00000437508.7	c.-49+51013T>C		intron_variant		1		ENSP00000415812	P3
TRIM2	ENST00000674874.1	c.-52+51671T>C		intron_variant				ENSP00000502519	P3
TRIM2	ENST00000675315.1	c.-49+51671T>C		intron_variant				ENSP00000502676	P3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64845 AN: 151988 Hom.: 18194 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.427 AC: 64953 AN: 152106 Hom.: 18248 Cov.: 32 AF XY: 0.424 AC XY: 31541 AN XY: 74368

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.387

Alfa AF: 0.356 Hom.: 1684

Bravo AF: 0.445

Asia WGS AF: 0.357 AC: 1240 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 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.40

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: rs28754692; hg19: chr4-154125435;