chr4-153270129-T-C

Position:

• chr4-153270129-T-C

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.31-206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,652 control chromosomes in the GnomAD database, including 4,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4568 hom., cov: 31)
• Consequence: TRIM2 NM_015271.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.718

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=-0.99).
• BP6: Variant 4-153270129-T-C is Benign according to our data. Variant chr4-153270129-T-C is described in ClinVar as [Benign]. Clinvar id is 1231381.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM2	NM_015271.5	c.31-206T>C		intron_variant		ENST00000338700.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM2	ENST00000338700.10	c.31-206T>C		intron_variant		1	NM_015271.5

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34962 AN: 151534 Hom.: 4564 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.231 AC: 34970 AN: 151652 Hom.: 4568 Cov.: 31 AF XY: 0.234 AC XY: 17335 AN XY: 74092

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.244

Alfa AF: 0.176 Hom.: 421

Bravo AF: 0.207

Asia WGS AF: 0.264 AC: 919 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	-0.99
CADD	Benign	5.2
DANN	Benign	0.16

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: rs2119163; hg19: chr4-154191281;