Genetic Variant TRAF3IP1:c.*489A>T (chr2-238399408-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015650.4(TRAF3IP1):c.*489A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 152,788 control chromosomes in the GnomAD database, including 413 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 0.067 ( 412 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1 hom. )

Consequence

TRAF3IP1
NM_015650.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.318

Publications

9 publications found

Variant links:

Genes affected

TRAF3IP1 (HGNC:17861): (TRAF3 interacting protein 1) The protein encoded by this gene interacts with TNF receptor-associated factor 3, tethering it to cytoskeletal microtubules. The encoded protein is also an inhibitor of the innate type I IFN response. Defects in this gene are a cause of Senior-Loken syndrome 9. [provided by RefSeq, Mar 2017]

TRAF3IP1 Gene-Disease associations (from GenCC):

Senior-Loken syndrome 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Majewski type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRAF3IP1 links:

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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 (NFE) allele frequency at 95% confidence interval = 0.0795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4 link	c.*489A>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000373327.5	NP_056465.2	Q8TDR0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3IP1	ENST00000373327.5 link	c.*489A>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_015650.4	ENSP00000362424.4		Q8TDR0-1
TRAF3IP1	ENST00000391993.7 link	c.*489A>T		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000375851.3		Q8TDR0-2

Frequencies

GnomAD3 genomes

AF:

0.0669

AC:

10179

AN:

152160

Hom.:

412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0412

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0428

Gnomad ASJ

AF:

0.0478

Gnomad EAS

AF:

0.0463

Gnomad SAS

AF:

0.0454

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0813

Gnomad OTH

AF:

0.0593

GnomAD4 exome

AF:

0.0451

AC:

AN:

510

Hom.:

Cov.:

AF XY:

0.0610

AC XY:

AN XY:

246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0283

AC:

AN:

106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0520

AC:

AN:

346

Other (OTH)

AF:

0.100

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0669

AC:

10182

AN:

152278

Hom.:

412

Cov.:

AF XY:

0.0678

AC XY:

5045

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0411

AC:

1709

AN:

41546

American (AMR)

AF:

0.0428

AC:

654

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0478

AC:

166

AN:

3472

East Asian (EAS)

AF:

0.0462

AC:

240

AN:

5192

South Asian (SAS)

AF:

0.0456

AC:

220

AN:

4822

European-Finnish (FIN)

AF:

0.142

AC:

1506

AN:

10600

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0813

AC:

5528

AN:

68028

Other (OTH)

AF:

0.0601

AC:

127

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

481

963

1444

1926

2407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0348

Hom.:

Bravo

AF:

0.0580

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.3

(source)

DANN

Benign

0.85

PhyloP100

-0.32

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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2-238399408-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over