rs12081405

chr1-209778921-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025228.4(TRAF3IP3):c.1253-394T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 227,208 control chromosomes in the GnomAD database, including 912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (612 hom., cov: 32)
  • Exomes 𝑓: 0.043 (300 hom.)
• Consequence: TRAF3IP3 NM_025228.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933

Genes affected

TRAF3IP3 (HGNC:30766): (TRAF3 interacting protein 3) The gene encodes a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. The encoded protein may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3IP3	NM_025228.4	c.1253-394T>A		intron_variant		ENST00000367025.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.1253-394T>A		intron_variant		1	NM_025228.4	P1

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6267 AN: 152158 Hom.: 606 Cov.: 32

Gnomad AFR AF: 0.00671

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0345

GnomAD4 exome AF: 0.0428 AC: 3205 AN: 74930 Hom.: 300 Cov.: 0 AF XY: 0.0465 AC XY: 1858 AN XY: 39956

Gnomad4 AFR exome AF: 0.00340

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.0163

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.0735

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.0134

Gnomad4 OTH exome AF: 0.0319

GnomAD4 genome AF: 0.0412 AC: 6278 AN: 152278 Hom.: 612 Cov.: 32 AF XY: 0.0471 AC XY: 3505 AN XY: 74456

Gnomad4 AFR AF: 0.00669

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.0872

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0228 Hom.: 23

Bravo AF: 0.0532

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	12
Dann	Benign	0.79

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: rs12081405; hg19: chr1-209952266;