rs12083685

Variant names:

• chr1-209778257-G-A
• rs12083685
• NM_025228.4:c.1252+84G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 3 publications found

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP3	NM_025228.4	c.1252+84G>A		intron_variant	Intron 13 of 16	ENST00000367025.8	NP_079504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.1252+84G>A		intron_variant	Intron 13 of 16	1	NM_025228.4	ENSP00000355992.3

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13823 AN: 152060 Hom.: 1306 Cov.: 32

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.: 13 AF XY: 0.0448 AC XY: 22580 AN XY: 503882

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: 87 AN: 4834

European-Non Finnish (NFE) AF: 0.0140 AC: 9608 AN: 686340

Other (OTH) AF: 0.0527 AC: 2317 AN: 43992

GnomAD4 genome AF: 0.0910 AC: 13848 AN: 152176 Hom.: 1313 Cov.: 32 AF XY: 0.0936 AC XY: 6961 AN XY: 74402

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: 76 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: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0140 AC: 954 AN: 68002

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.60
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12083685; hg19: chr1-209951602; COSMIC: COSV107207153; COSMIC: COSV107207153;