dbSNP rs12081405: TRAF3IP3:c.1253-394T>A (chr1-209778921-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.933

Publications

1 publications found

Variant links:

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]

TRAF3IP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAF3IP3	NM_025228.4	MANE Select	c.1253-394T>A	intron	N/A	NP_079504.2	Q9Y228-1
TRAF3IP3	NM_001320143.2		c.1253-394T>A	intron	N/A	NP_001307072.1	Q9Y228-1
TRAF3IP3	NM_001320144.2		c.1193-394T>A	intron	N/A	NP_001307073.1	Q9Y228-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAF3IP3	ENST00000367025.8	TSL:1 MANE Select	c.1253-394T>A	intron	N/A	ENSP00000355992.3	Q9Y228-1
TRAF3IP3	ENST00000367026.7	TSL:1	c.1193-394T>A	intron	N/A	ENSP00000355993.3	Q9Y228-2
TRAF3IP3	ENST00000478359.5	TSL:1	n.*55-394T>A	intron	N/A	ENSP00000417665.1	Q9Y228-3

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6267

AN:

152158

Hom.:

606

Cov.:

show subpopulations

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.:

AF XY:

0.0465

AC XY:

1858

AN XY:

39956

show subpopulations

African (AFR)

AF:

0.00340

AC:

AN:

1178

American (AMR)

AF:

0.198

AC:

753

AN:

3800

Ashkenazi Jewish (ASJ)

AF:

0.0163

AC:

AN:

1898

East Asian (EAS)

AF:

0.310

AC:

783

AN:

2524

South Asian (SAS)

AF:

0.0735

AC:

825

AN:

11218

European-Finnish (FIN)

AF:

0.0158

AC:

AN:

3490

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.0134

AC:

626

AN:

46598

Other (OTH)

AF:

0.0319

AC:

126

AN:

3956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

137

274

412

549

686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0412

AC:

6278

AN:

152278

Hom.:

612

Cov.:

AF XY:

0.0471

AC XY:

3505

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00669

AC:

278

AN:

41572

American (AMR)

AF:

0.181

AC:

2774

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3472

East Asian (EAS)

AF:

0.312

AC:

1612

AN:

5160

South Asian (SAS)

AF:

0.0872

AC:

420

AN:

4816

European-Finnish (FIN)

AF:

0.0126

AC:

134

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0133

AC:

905

AN:

68030

Other (OTH)

AF:

0.0346

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

250

500

750

1000

1250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0532

Asia WGS

AF:

0.154

AC:

534

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.93

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over