Menu
GeneBe

rs17854985

chr2-238329333-T-Cchr2-238329333-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015650.4(TRAF3IP1):c.906T>C(p.Pro302=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,357,820 control chromosomes in the GnomAD database, including 4,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P302P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.12 ( 1753 hom., cov: 32)
Exomes 𝑓: 0.052 ( 2680 hom. )

Consequence

TRAF3IP1
NM_015650.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.68
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-238329333-T-C is Benign according to our data. Variant chr2-238329333-T-C is described in ClinVar as [Benign]. Clinvar id is 1167551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.68 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRAF3IP1NM_015650.4 linkuse as main transcriptc.906T>C p.Pro302= synonymous_variant 5/17 ENST00000373327.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRAF3IP1ENST00000373327.5 linkuse as main transcriptc.906T>C p.Pro302= synonymous_variant 5/171 NM_015650.4 Q8TDR0-1
TRAF3IP1ENST00000391993.7 linkuse as main transcriptc.906T>C p.Pro302= synonymous_variant 5/151 P1Q8TDR0-2
TRAF3IP1ENST00000409739.2 linkuse as main transcriptc.*775T>C 3_prime_UTR_variant, NMD_transcript_variant 5/53

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.116
AC:
17696
AN:
151986
Hom.:
1748
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.268
Gnomad AMI
AF:
0.0285
Gnomad AMR
AF:
0.0815
Gnomad ASJ
AF:
0.0473
Gnomad EAS
AF:
0.103
Gnomad SAS
AF:
0.113
Gnomad FIN
AF:
0.114
Gnomad MID
AF:
0.0665
Gnomad NFE
AF:
0.0394
Gnomad OTH
AF:
0.0980
GnomAD3 exomes
AF:
0.0804
AC:
10662
AN:
132600
Hom.:
739
AF XY:
0.0752
AC XY:
5357
AN XY:
71206
show subpopulations
Gnomad AFR exome
AF:
0.263
Gnomad AMR exome
AF:
0.0730
Gnomad ASJ exome
AF:
0.0404
Gnomad EAS exome
AF:
0.107
Gnomad SAS exome
AF:
0.100
Gnomad FIN exome
AF:
0.106
Gnomad NFE exome
AF:
0.0401
Gnomad OTH exome
AF:
0.0807
GnomAD4 exome
AF:
0.0516
AC:
62170
AN:
1205716
Hom.:
2680
Cov.:
32
AF XY:
0.0515
AC XY:
29862
AN XY:
579336
show subpopulations
Gnomad4 AFR exome
AF:
0.281
Gnomad4 AMR exome
AF:
0.0757
Gnomad4 ASJ exome
AF:
0.0422
Gnomad4 EAS exome
AF:
0.111
Gnomad4 SAS exome
AF:
0.0967
Gnomad4 FIN exome
AF:
0.101
Gnomad4 NFE exome
AF:
0.0384
Gnomad4 OTH exome
AF:
0.0653
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.117
AC:
17728
AN:
152104
Hom.:
1753
Cov.:
32
AF XY:
0.119
AC XY:
8838
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.268
Gnomad4 AMR
AF:
0.0817
Gnomad4 ASJ
AF:
0.0473
Gnomad4 EAS
AF:
0.102
Gnomad4 SAS
AF:
0.113
Gnomad4 FIN
AF:
0.114
Gnomad4 NFE
AF:
0.0394
Gnomad4 OTH
AF:
0.0970
Alfa
AF:
0.0314
Hom.:
34
Bravo
AF:
0.120
Asia WGS
AF:
0.0980
AC:
341
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 05, 2021- -
TRAF3IP1-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 21, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
Cadd
Benign
0.047
Dann
Benign
0.16
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17854985; hg19: chr2-239237974; COSMIC: COSV64852069; API