Genetic Variant NM_025228.4:c.1252+84G>A (chr1-209778257-G-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.1252+84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 1,128,674 control chromosomes in the GnomAD database, including 5,691 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 0.091 ( 1313 hom., cov: 32)

Exomes 𝑓: 0.046 ( 4378 hom. )

Consequence

TRAF3IP3
NM_025228.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Publications

3 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 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.1252+84G>A	intron	N/A	NP_079504.2	Q9Y228-1
TRAF3IP3	NM_001320143.2		c.1252+84G>A	intron	N/A	NP_001307072.1	Q9Y228-1
TRAF3IP3	NM_001320144.2		c.1192+84G>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.1252+84G>A	intron	N/A	ENSP00000355992.3	Q9Y228-1
TRAF3IP3	ENST00000367026.7	TSL:1	c.1192+84G>A	intron	N/A	ENSP00000355993.3	Q9Y228-2
TRAF3IP3	ENST00000478359.5	TSL:1	n.*54+84G>A	intron	N/A	ENSP00000417665.1	Q9Y228-3

Frequencies

GnomAD3 genomes

AF:

0.0909

AC:

13823

AN:

152060

Hom.:

1306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.0879

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.0727

GnomAD4 exome

AF:

0.0461

AC:

45014

AN:

976498

Hom.:

4378

Cov.:

AF XY:

0.0448

AC XY:

22580

AN XY:

503882

show subpopulations

African (AFR)

AF:

0.180

AC:

4063

AN:

22570

American (AMR)

AF:

0.269

AC:

10091

AN:

37444

Ashkenazi Jewish (ASJ)

AF:

0.0247

AC:

543

AN:

22006

East Asian (EAS)

AF:

0.338

AC:

11919

AN:

35252

South Asian (SAS)

AF:

0.0778

AC:

5628

AN:

72350

European-Finnish (FIN)

AF:

0.0147

AC:

758

AN:

51710

Middle Eastern (MID)

AF:

0.0180

AC:

AN:

4834

European-Non Finnish (NFE)

AF:

0.0140

AC:

9608

AN:

686340

Other (OTH)

AF:

0.0527

AC:

2317

AN:

43992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1806

3611

5417

7222

9028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.0910

AC:

13848

AN:

152176

Hom.:

1313

Cov.:

AF XY:

0.0936

AC XY:

6961

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.178

AC:

7376

AN:

41498

American (AMR)

AF:

0.202

AC:

3095

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3470

East Asian (EAS)

AF:

0.311

AC:

1607

AN:

5160

South Asian (SAS)

AF:

0.0871

AC:

420

AN:

4822

European-Finnish (FIN)

AF:

0.0126

AC:

134

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0140

AC:

954

AN:

68002

Other (OTH)

AF:

0.0724

AC:

153

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

562

1123

1685

2246

2808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0516

Hom.:

219

Bravo

AF:

0.109

Asia WGS

AF:

0.164

AC:

569

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.29

(source)

DANN

Benign

0.60

PhyloP100

-1.2

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