rs590223

chr1-209773362-G-A

Variant summary

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

The NM_025228.4(TRAF3IP3):c.774+343G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,090 control chromosomes in the GnomAD database, including 29,248 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 0.62 (29248 hom., cov: 33)
• Consequence: TRAF3IP3 NM_025228.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3IP3	NM_025228.4	c.774+343G>A		intron_variant		ENST00000367025.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.774+343G>A		intron_variant		1	NM_025228.4	P1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93927 AN: 151972 Hom.: 29228 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.618 AC: 94001 AN: 152090 Hom.: 29248 Cov.: 33 AF XY: 0.618 AC XY: 45953 AN XY: 74346

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.631

Alfa AF: 0.625 Hom.: 13517

Bravo AF: 0.620

Asia WGS AF: 0.574 AC: 1997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.0
Dann	Benign	0.20

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: rs590223; hg19: chr1-209946707;