rs590223

Variant names:

• chr1-209773362-G-A
• rs590223
• NM_025228.4:c.774+343G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025228.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP3	NM_025228.4	MANE Select	c.774+343G>A		intron	N/A	NP_079504.2	Q9Y228-1
	TRAF3IP3	NM_001320143.2		c.774+343G>A		intron	N/A	NP_001307072.1	Q9Y228-1
	TRAF3IP3	NM_001320144.2		c.714+343G>A		intron	N/A	NP_001307073.1	Q9Y228-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP3	ENST00000367025.8	TSL:1 MANE Select	c.774+343G>A		intron	N/A	ENSP00000355992.3	Q9Y228-1
	TRAF3IP3	ENST00000367026.7	TSL:1	c.714+343G>A		intron	N/A	ENSP00000355993.3	Q9Y228-2
	TRAF3IP3	ENST00000478359.5	TSL:1	n.774+343G>A		intron	N/A	ENSP00000417665.1	Q9Y228-3

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

African (AFR) AF: 0.572 AC: 23738 AN: 41470

American (AMR) AF: 0.670 AC: 10234 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2430 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3318 AN: 5170

South Asian (SAS) AF: 0.558 AC: 2685 AN: 4812

European-Finnish (FIN) AF: 0.632 AC: 6688 AN: 10582

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42852 AN: 67986

Other (OTH) AF: 0.631 AC: 1333 AN: 2112

Alfa AF: 0.624 Hom.: 15002

Bravo AF: 0.620

Asia WGS AF: 0.574 AC: 1997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.20
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs590223; hg19: chr1-209946707;