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rs13398676

chr2-238320731-C-Achr2-238320731-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015650.4(TRAF3IP1):c.69C>A(p.Thr23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 1,446,688 control chromosomes in the GnomAD database, including 372,651 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. T23T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.72 ( 39699 hom., cov: 33)
Exomes 𝑓: 0.71 ( 332952 hom. )

Consequence

TRAF3IP1
NM_015650.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.609
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 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=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-238320731-C-A is Benign according to our data. Variant chr2-238320731-C-A is described in ClinVar as [Benign]. Clinvar id is 1168003.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=-0.609 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 = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRAF3IP1NM_015650.4 linkuse as main transcriptc.69C>A p.Thr23= synonymous_variant 1/17 ENST00000373327.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRAF3IP1ENST00000373327.5 linkuse as main transcriptc.69C>A p.Thr23= synonymous_variant 1/171 NM_015650.4 Q8TDR0-1
TRAF3IP1ENST00000391993.7 linkuse as main transcriptc.69C>A p.Thr23= synonymous_variant 1/151 P1Q8TDR0-2
TRAF3IP1ENST00000409739.2 linkuse as main transcriptc.69C>A p.Thr23= synonymous_variant, NMD_transcript_variant 1/53

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.723
AC:
109206
AN:
151060
Hom.:
39660
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.729
Gnomad AMI
AF:
0.665
Gnomad AMR
AF:
0.702
Gnomad ASJ
AF:
0.789
Gnomad EAS
AF:
0.476
Gnomad SAS
AF:
0.681
Gnomad FIN
AF:
0.844
Gnomad MID
AF:
0.787
Gnomad NFE
AF:
0.724
Gnomad OTH
AF:
0.737
GnomAD3 exomes
AF:
0.725
AC:
72412
AN:
99838
Hom.:
26737
AF XY:
0.724
AC XY:
39707
AN XY:
54856
show subpopulations
Gnomad AFR exome
AF:
0.701
Gnomad AMR exome
AF:
0.711
Gnomad ASJ exome
AF:
0.783
Gnomad EAS exome
AF:
0.441
Gnomad SAS exome
AF:
0.698
Gnomad FIN exome
AF:
0.842
Gnomad NFE exome
AF:
0.719
Gnomad OTH exome
AF:
0.719
GnomAD4 exome
AF:
0.715
AC:
925850
AN:
1295520
Hom.:
332952
Cov.:
56
AF XY:
0.716
AC XY:
457730
AN XY:
639182
show subpopulations
Gnomad4 AFR exome
AF:
0.735
Gnomad4 AMR exome
AF:
0.709
Gnomad4 ASJ exome
AF:
0.779
Gnomad4 EAS exome
AF:
0.475
Gnomad4 SAS exome
AF:
0.695
Gnomad4 FIN exome
AF:
0.834
Gnomad4 NFE exome
AF:
0.715
Gnomad4 OTH exome
AF:
0.712
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.723
AC:
109295
AN:
151168
Hom.:
39699
Cov.:
33
AF XY:
0.724
AC XY:
53489
AN XY:
73862
show subpopulations
Gnomad4 AFR
AF:
0.729
Gnomad4 AMR
AF:
0.703
Gnomad4 ASJ
AF:
0.789
Gnomad4 EAS
AF:
0.475
Gnomad4 SAS
AF:
0.682
Gnomad4 FIN
AF:
0.844
Gnomad4 NFE
AF:
0.724
Gnomad4 OTH
AF:
0.738
Alfa
AF:
0.719
Hom.:
16347
Bravo
AF:
0.716
Asia WGS
AF:
0.616
AC:
1961
AN:
3176

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 testingGeneDxNov 12, 2018- -
Senior-Loken syndrome 9 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
11
Dann
Benign
0.93
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: rs13398676; hg19: chr2-239229372; COSMIC: COSV64852392; API